Article

Implantable Biodegradable Sponges: Effect of Interpolymer Complex Formation of Chitosan With Gelatin on the Release Behavior of Tramadol Hydrochloride

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The effect of interpolymer complex formation between positively charged chitosan and negatively charged gelatin (Type B) on the release behavior of tramadol hydrochloride from biodegradable chitosan-gelatin sponges was studied. Mixed sponges were prepared by freeze-drying the cross-linked homogenous stable foams produced from chitosan and gelatin solutions where gelatin acts as a foam builder. Generation of stable foams was optimized where concentration, pH of gelatin solution, temperature, speed and duration of whipping process, and, chitosan-gelatin ratio drastically affect the properties and the stability of the produced foams. The prepared sponges were evaluated for their morphology, drug content, and microstructure using scanning electron microscopy, mechanical properties, uptake capacity, drug release profile, and their pharmacodynamic activity in terms of the analgesic effect after implantation in Wistar rats. It was revealed that whipping 7% (w/w) gelatin solution, of pH 5.5, for 15 min at 25 degrees C with a stirring speed of 1000 rpm was the optimum conditions for stable gelatin foam generation. Moreover, homogenous, uniform chitosan-gelatin foam with small air bubbles were produced by mixing 2.5% w/w chitosan solution with 7% w/w gelatin solution in 1:5 ratio. Indeed, polyionic complexation between chitosan and gelatin overcame the drawbacks of chitosan sponge mechanical properties where, pliable, soft, and compressible sponge with high fluid uptake capacity was produced at 25 degrees C and 65% relative humidity without any added plasticizer. Drug release studies showed a successful retardation of the incorporated drug where the t50% values of the dissolution profiles were 0.55, 3.03, and 4.73 hr for cross-linked gelatin, un-cross-linked chitosan-gelatin, and cross-linked chitosan-gelatin sponges, respectively. All the release experiments followed Higuchi's diffusion mechanism over 12 hr. The achieved drug prolongation was a result of a combined effect of both cross-linking and polyelectrolyte complexation between chitosan and gelatin. The analgesic activity of the implanted tramadol hydrochloride mixed chitosan-gelatin sponge showed reasonable analgesic effect that was maintained for more than 8 hr. Therefore, the use of chitosan and gelatin together appears to allow the formulator to manipulate both the drug release profiles and the mechanical properties of the sponge that could be effectively implanted.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... In vivo degradation of chitosan is carried out by lysozymes along with wide-range of hydrolytic enzymes (present in lymphoid tissues) which are capable of hydrolyzing the polymer [163,164]. Upon degradation inside the human system, amino sugars are formed which are eventually processed and released into the metabolic system [165]. Few enzymes capable of degrading chitosan possess well defined structural skeleton but their mechanism of action is yet to be unraveled. ...
... Few enzymes capable of degrading chitosan possess well defined structural skeleton but their mechanism of action is yet to be unraveled. However, these enzymes are not present in animals and when chitosan is disseminated in their system, will subsequently disappear in due course of time showing a correlation between the degree of deacetylation and rate of degradation [165]. Chemical degradation (enzymatic hydrolysis) can be used to easily hydrolyze chitosan owing to the highly susceptible glycosidic bonds felicitated by hydrolases viz., lysozymes, cellulasese, pectinase, lipases along with amylases and hemicellulases indicating unique susceptibility to enzymes other than chitinase. ...
... Degradation products include oligosaccharides, monosaccharides and metabolic product of glycosaminoglycans. Lysozyme (proteolytic enzyme) can efficiently hydrolyze chitosan but fails to perform when the degree of acetylation is below 30% [165]. Chitosan shows complete resistant against lysozyme in fully acetylated form. ...
Chapter
Full-text available
Natural polymers offer an unrivaled potential and are poised to become the next major commercial breakthrough in the arena of pharmaceutical industry, novel drug delivery, biotechnological and biomedical application in terms of product safety, cost-effectiveness, therapeutic value and eco-friendly nature. At this juncture , it is imperative to mention the application of natural polymers in wound healing which are of vital interest for research owing to its magnificent biocom-patibility and therapeutic potential. Chitosan is an exclusively natural biopoly-mer comprising of two subunits, D-glucosamine (deacetylated) and N-acetyl-D-glucosamine (acetylated) linked via 1, 4-glycosidic bonds. It is one of the second most abundant natural polysaccharide and mainly obtained from the exoskeleton of crustaceans. Chitosan is an undisputed molecule of great potential and finds application in a variety of industries such as food, cosmetics, textiles, paper and pharmaceuticals due to its inherent properties such as non-toxic, non-irritant, mechanical stability, renewability, availability at low cost, ease of modification and low immunogenicity. Chitosan possesses structural characteristics similar to gly-cosamine glycans, used to develop tissue-engineered matrices and substratum to replace skin grafts. Electrostatic property of chitosan helps in stimulating collagen synthesis and fibroblast growth followed by initiation of early phase reaction pathways associated with accelerated wound healing process. It is extensively employed in the development of novel dressing material to assess its wound healing potential due to its biocompatibility, biodegradability, antimicrobial, non-antigenic, film
... In vivo degradation of chitosan is carried out by lysozymes along with wide-range of hydrolytic enzymes (present in lymphoid tissues) which are capable of hydrolyzing the polymer [163,164]. Upon degradation inside the human system, amino sugars are formed which are eventually processed and released into the metabolic system [165]. Few enzymes capable of degrading chitosan possess well defined structural skeleton but their mechanism of action is yet to be unraveled. ...
... Few enzymes capable of degrading chitosan possess well defined structural skeleton but their mechanism of action is yet to be unraveled. However, these enzymes are not present in animals and when chitosan is disseminated in their system, will subsequently disappear in due course of time showing a correlation between the degree of deacetylation and rate of degradation [165]. Chemical degradation (enzymatic hydrolysis) can be used to easily hydrolyze chitosan owing to the highly susceptible glycosidic bonds felicitated by hydrolases viz., lysozymes, cellulasese, pectinase, lipases along with amylases and hemicellulases indicating unique susceptibility to enzymes other than chitinase. ...
... Degradation products include oligosaccharides, monosaccharides and metabolic product of glycosaminoglycans. Lysozyme (proteolytic enzyme) can efficiently hydrolyze chitosan but fails to perform when the degree of acetylation is below 30% [165]. Chitosan shows complete resistant against lysozyme in fully acetylated form. ...
Chapter
Full-text available
Natural polymers offers an unrivalled potential and are poised to become the next major commercial breakthrough in the arena of pharmaceutical industry, novel drug delivery, biotechnological and biomedical application in terms of product safety, cost-effectiveness, therapeutic value and eco-friendly nature. At this juncture, it is imperative to mention the application of natural polymers in wound healing which are of vital interest for research owing to its magnificent biocompatibility and therapeutic potential. Chitosan is an exclusively natural biopolymer comprising of two subunits, D-glucosamine (deacetylated) and N-acetyl-D-glucosamine (acetylated) linked via 1, 4-glycosidic bonds. It is one of the second most abundant natural polysaccharide and mainly obtained from exoskeleton of crustaceans. Chitosan is an undisputed molecule of great potential and finds application in a variety of industries such as food, cosmetics, textiles, paper and pharmaceuticals due to its inherent properties such as non-toxic, non-irritant, mechanical stability, renewability, availability at low cost, ease of modification and low immunogenicity. Chitosan possess structural characteristics similar to glycosamine glycans, used to develop tissue engineered matrices and substratum to replace skin grafts. Electrostatic property of chitosan helps in stimulating collagen synthesis and fibroblast growth followed by initiation of early phase reaction pathways associated with accelerated wound healing process. It is extensively employed in development of novel dressing material to assess its wound healing potential due to its biocompatibility, biodegradability, antimicrobial, non-antigenic, film forming, tensile strength and hemostatic effect. Undoubtedly, Chitosan is a natural “wonder molecule” exploited in the commercial and biomedical fields due to its invincible characteristics and unique properties. This chapter aims to provide a brief insight into wound healing potential of chitosan along with its derivatives and conjugates.
... Chitosan has many physical and chemical properties conferred by its functional groups (amino NH2 and hydroxyl OH), as well as biological properties coming from its chemical composition. Solubility, biodegradability, reactivity, and absorption of many of its substrates depend on the amount of protonated amino groups in the polymer chain and thus in the rate of acetylated or nonacetylated glucosamine [35,36]. All of these features make it an attractive option for several applications in science such as food/nutrition, medicine, microbiology, immunology, agriculture, and veterinary medicine [37]. ...
... Inside the body it leads to the release of amino sugars that can be processed and released by the metabolic system. Chitosan degradation is an important property assuming that the end processes and applications it will ultimately be given can agree with the resulting design [35]. ...
... Some of the specific enzymes that degrade chitin and chitosan have a clearly identified structure but their action mechanisms are still unknown. In mammals, these enzymes seem to be completely absent; however, when chitosan is implanted, it will eventually disappear completely after some time and the degradation speed seems to depend on DD [35]. ...
Article
Full-text available
Tissue engineering is an important therapeutic strategy to be used in regenerative medicine in the present and in the future. Functional biomaterials research is focused on the development and improvement of scaffolding, which can be used to repair or regenerate an organ or tissue. Scaffolds are one of the crucial factors for tissue engineering. Scaffolds consisting of natural polymers have recently been developed more quickly and have gained more popularity. These include chitosan, a copolymer derived from the alkaline deacetylation of chitin. Expectations for use of these scaffolds are increasing as the knowledge regarding their chemical and biological properties expands, and new biomedical applications are investigated. Due to their different biological properties such as being biocompatible, biodegradable, and bioactive, they have given the pattern for use in tissue engineering for repair and/or regeneration of different tissues including skin, bone, cartilage, nerves, liver, and muscle. In this review, we focus on the intrinsic properties offered by chitosan and its use in tissue engineering, considering it as a promising alternative for regenerative medicine as a bioactive polymer.
... Chitosan has many physicochemical (reactive OH and NH 2 groups) and biological (biocompatible, biodegradable) properties that make it an attractive material for use in various applications. These properties include: biodegradability, lack of toxicity, anti-fungal effects, wound healing acceleration, and immune system stimulation [24][25][26]. Because of chitosan's biological and chemical properties it has the ability to bind to particular materials including cholesterols, fats, proteins, metal ions, and even tumor cells. ...
... Within the body the degradation of chitosan leads to the release of aminosugars, which can be easily processed and released through the metabolic system. Degradation is an important property to understand so that processing and end applications can be designed accordingly [26]. ...
... Due to chitosan's ability to function in many forms it has many areas of interest within the medical industry including: orthopedic, tissue engineering, wound healing, drug delivery, and surgical adhesion [25][26][27]. ...
Article
Chitosan is a safe and friendly substance for the human organism; therefore, it has become of great interest not only as an underutilized resource, but also as a new functional material of high potential in various fields. Some unique properties make chitosan an excellent material for the development of new industrial applications and recent progress in chitosan material is quite noteworthy. In this review, we mainly take a closer look at various chitosan applications and intend to provide interdisciplinary insight in the scientific knowledge immediately usable to realize fabrications. In addition, based on current research and existing products, some new approaches in this fascinating area are thoroughly discussed
... [13] The last decade has seen a growing interest in using polyelectrolyte complexes (PEC) in material design for cell culture. PEC formed materials using chitosan together with heparin, [14,15] hyaluronic acid with chondroitin sulfate, [16] or gelatin [17][18][19][20] with alginic acid [21] have all proven to have great potential in tissue engineering. The advantage of having a structure based on PEC is that, at physiological pH, the surface of the material is partly charged. ...
... Previously, it has been reported that, as a result of PEC formation, the morphology of the surface of pore walls is significantly changed from smooth to a more textured surface, [15] which was also seen for our sample CHI-OxD-Gel when analyzed using SEM (Figure 2a). It is well-known that chitosan and gelatin form PEC and has been shown [18,20,30,31] to have importance for practical applications in, for example, drug delivery systems or the formation of nanofibers. [17,18,29] Recently, it was further shown in a study that a sample made from 1.0 wt% CHI, 4.0 wt% Gel and 0.5 wt% GA appeared to produce a smooth pore wall texture. ...
... It is well-known that chitosan and gelatin form PEC and has been shown [18,20,30,31] to have importance for practical applications in, for example, drug delivery systems or the formation of nanofibers. [17,18,29] Recently, it was further shown in a study that a sample made from 1.0 wt% CHI, 4.0 wt% Gel and 0.5 wt% GA appeared to produce a smooth pore wall texture. [23] It might be that glutaraldehyde, which is highly reactive, crosslinked the structure before PEC were able to form. ...
Article
Macroporous scaffolds composed of chitosan and using oxidized dextran as a crosslinker are produced through cryogelation. Introducing gelatin as a third component into the structure results in the formation of mesopores in the pore walls, which are not seen if gelatin is excluded. The mesoporous structure is explained by the formation of polyelectrolyte complexes between chitosan and gelatin before crosslinking takes place. The scaffolds exhibit highly elastic properties withstanding compressions up to 60%. The in vitro biocompatibility of the cryogels is evaluated using fibroblasts from a mouse cell line (L929) and it is seen that the cells adhere and proliferate on the scaffolds. The mesoporous structure seems to have a positive effect on proliferation. Current address for correspondence: e-mail dmitryi.berillo@nu.edu.kz; Laboratory of Biosensors and Bioinstruments, PI" National Laboratory Astana", Nazarbaev University, 53 Kabanbay batyr ave., Astana, 010000, Republic of Kazakhstan.
... 65 Fig. 7c shows the dense porous structure of chitosan-lactate hyaluronate sponge reported in this study [65]. Pores are randomly organized all across the surface while b indicates elliptical regularly arranged pores Fig. 7 in chitosan-gelatin sponge [66]. This is of considerable importance from the drug delivery perspective because the drug is impregnated inside sponge dressing for controlled and sustained release. ...
... They have randomly organized dense porous structures [57]. Results of these studies show that presence of gelatin in combination with Mechan-66 ical properties of chitosan was also improved due to the addition of gelatin and the sponges produced were comparatively soft, flexible and compressible with augmented moisture sorption ability [66]. Chitosan and gelatin sponges were prepared by him through freeze drying method whereas the factor affecting stability of foam were chitosan-gelatin ratio, whipping speed, duration and temperature as well as pH of gelatin solution. ...
... Chitosan and gelatin sponges were prepared by him through freeze drying method whereas the factor affecting stability of foam were chitosan-gelatin ratio, whipping speed, duration and temperature as well as pH of gelatin solution. He further indicated that storing these sponges at 43-65 % relative humidity retains its pliability while the best compressibility is achieved with chitosan sponges stored at 65% relative humidity [66]. Results of this study suggest that the used formulation of chitosan-gelatin sponge can be well-adapted for wound healing purpose and it requires further in-vitro and in-vivo studies. ...
... Subcutaneous implants of these formulations in rats showed reasonable analgesic effect that could be maintained for more than 8 h. Furthermore, the polyelectrolyte complex between chitosan and gelatin produced sponges with improved mechanical properties compared to sponges containing chitosan alone [10]. ...
... .(10). Morphology of chitosan-dextran sulfate (CS-DS) hydrogel by emission scanning electron microscopy field. ...
Article
Full-text available
The purpose of this review is to discuss and summarize some of the interesting findings and applications of modified chitosan (MCS) and their derivatives in different areas of drug delivery. This review highlights the important applications of MCS in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their uses as recipients in drug formulation are also discussed. This review also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting MCS in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized.
... Gelatin (Gel) is biodegradable, nontoxic and inexpensive protein, which at low temperature, and pH spontaneously forms nonimmunogenic physical hydrogel [3]. It has been extensively used in combination with other polymers and cross-linkers [5,6] for the preparation of materials for medical purposes [7] and tissue engineering [4,6,8,9]. ...
... The second batch was prepared at pH 8(IEP of Gel), these pH gelatin macromolecules have globular or socalled compact conformation [9,35]. The rate of deliquescence of freshly thawed cryogels (pH 8) was lower than at pH 5.2, but the mechanical properties were not improved and did not allow the reliable measurements of the elastic modulus. ...
Article
Full-text available
In this study, a novel method of preparation of cryogels based on oxidised dextran (Ox.D) and gelatin (Gel) without sodium borohydride is proposed. The physico-chemical properties of obtained hydrogels were investigated. It was found that the stability of cryogels Ox.D–Gel is significantly depended on pH, and mechanical properties were improved after the freeze drying. The schemes of the reactions between Ox.D and Gel at different steps of the treatment of the material were suggested. According to 1H-NMR data, the Amadori rearrangement occurred under the step of cryogelation. The increase of cross-linking degree through the formation of additional Schiff’s base group was observed as a result of incubation at high humidities or elevated temperature (60 °C). The obtained cryogels can be used as biocompatible and biodegradable scaffolds for proliferation of cells or other biomedical applications. Current address for correspondence: e-mail dmitryi.berillo@nu.edu.kz; Laboratory of Biosensors and Bioinstruments, PI" National Laboratory Astana", Nazarbaev University, 53 Kabanbay batyr ave., Astana, 010000, Republic of Kazakhstan.
... Chitosan has many physico-chemical (solubility, viscosity, crystallinity, reactivity, and adsorption) and biological characteristics that allow it as fascinating stuff in countless applications. The biological characteristics mainly include lack of toxicity, biodegradability, biocompatibility, cyto-compatibility, antimicrobial activity, fungicidal effects, haemostatic action, wound healing stimulation (Foda, El-laithy & Tadros, 2007;Khor & Lim, 2003;Li, Dunn, Grandmaison & Goosen, 1992). Chitosan has the exceptional ability to bind the specific materials including cholesterols, proteins, fats, tumor cells, 3.5% NaOH (w/v) at 65°C solid: solvent (1:10, w/v) metal ions, etc., because of its diversified biological and chemical properties (analgesic action, anti-cholestemic activity, antioxidant activity, anti-inflammatory activity, angiogenesis stimulation, macrophage activation, muco-adhesion, permeation enhancing effect, anti-tumor, granulation and scar formulation) (Kumirska, Weinhold, Thoming & Stepnowski, 2011b), attributing it to be used in innumerable applications, for instance in agriculture, food industry, medical, and environmental protection as a chelating agent (Åženel & McClure, 2004). ...
... An important property of chitosan is degradation to understand the processing; thus, the applications can be designed accordingly (Foda, El-laithy & Tadros, 2007). There are several influences that can degrade chitosan and it has been summarized that its degradation rate is inversely proportional to the degree of crystallinity, hence the amount of deacetylation. ...
Chapter
Adsorption is a procedure for treating wastewater, and an important tool for protecting the environment. In particular, adsorption on natural polymers and their derivatives are known to remove a wide variety of pollutants from water. Chitosan derivatives have gained wide attention as effective biosorbents due to low cost and high contents of amino and hydroxyl functional groups that show significant adsorption potential for the removal of different types of organic and inorganic pollutants. Chemical modifications that lead to the formation of chitosan derivatives, grafting chitosan and chitosan composites have gained much attention, extensively studied and widely reported in the literature. This review provides relevant literature on the application of chitosan derivatives for wastewater treatment. A list of chitosan composites with their adsorption capacity and the experimental conditions will be compiled. The main objective of this chapter is to provide recent information about the most important features of chitosan and to show the advantages gained from the use chitosan-modified adsorbents in wastewater treatment.
... Which indicated that the sodium alginate increasing the flexibility of scaffolds. Increased equilibrium swelling might be due to hydrophilicity and swelling property of sodium alginate [17,18] which is consistent with results of chitosan& gelatin 3,17 . It was also observed that the tensile and texture parameters were increased with increase in sodium alginate concentration (table no 2) which confirmed the enhanced mechanical property by composite scaffolds. ...
... Which indicated that the sodium alginate increasing the flexibility of scaffolds. Increased equilibrium swelling might be due to hydrophilicity and swelling property of sodium alginate [17,18] which is consistent with results of chitosan& gelatin 3,17 . It was also observed that the tensile and texture parameters were increased with increase in sodium alginate concentration (table no 2) which confirmed the enhanced mechanical property by composite scaffolds. ...
Article
Biopolymers are used as basic compounds for design of scaffolds for different tissue engineering applications. Chitosan and sodium alginate have proven wound healing property individually. But the scaffolds prepared with single polymer have shown poor physicomechanical properties which are essential during handling, storage and application. Hence, the present study focused on development of composite scaffolds using chitosan and different concentrations of sodium alginate to enhance the physico mechanical properties and also loaded with lentil seed extract (LSE) to improve its wound healing property with the combination of antioxidant/antibacterial activities of LSE. The LSE loaded composite scaffolds were prepared with different concentrations of ethanolic extract of lentil seeds in selected best blank composite scaffolds. All the scaffolds were evaluated for various in vitro parameters like thickness, folding endurance, equilibrium swelling, antibacterial activity, tensile and texture parameters to confirm the suitability of prepared external combination. The wound healing activity was determined by in vivo studies using albino rats by estimating percentage wound contraction, histopathological properties, biochemical parameters and photography. As the concentration of sodium alginate was increased the mechanical properties of scaffolds were remarkably improved. The LSE loaded scaffolds shown significant difference in antibacterial and wound healing activity when compared to blank composite scaffolds. The present results revealed that LSE loaded prepared bioscaffolds possessed fast wound healing activity compared to blank scaffolds without losing its mechanical properties. The present study successfully designed a natural, biocompatible wound dressing at low cost for fast healing of wounds in animals and human beings.
... In addition, it should be as low as possible with the consideration to achieve optimum values of desired properties of sponge. The biodegradable polymers currently used as sponge and scaffolds for similar purposes include chitosan, [17] chitosan-gelatin, [18,19] chitosan-alginate, [20] chitin, [21,22] collagen, [23,24] arabinogalactan, [25] alginate, [26] polyglycolide, polylactide and their copolymers, [27,28] hyaluronate, [22,29] and gelatin. [30] Porous biopolymers such as sponge based on naturally occurring biodegradable material can provide a frame to absorb wound fluid and promote healing. ...
... In addition to wound treatment, sponges may also serve as drug carriers. [18,31] Biopolymer used as wound dressings, hemostats, and scaffolds for tissue engineering in the forms of sponges are usually required to disappear by resorption into the body after accomplishment of tissue regeneration within a couple of weeks. [32] The foam may be produced by beating or otherwise mechanically agitating the material to cause the gelatin solution to foam. ...
Article
Full-text available
This research article pertains to a process for the preparation of lyophilized absorbable gelatin sponge. The Kenics static mixer was used for gelatin foam preparation and subsequently lyophilized in a freeze dryer. The lyophilized sponge was characterized for its pore size, bulk density, degree of cross-linking, mechanical stability, water absorption capacity, water intake rate, and thermal stability. The extent of cross-linking was evaluated by gelatin solubility test method. With increasing concentration of formaldehyde, Young's modulus and the stress at break increases and the strain at break decreases. Simultaneously, cross-linking provokes a significant reduction of swelling in water and it enhances the thermal stability of the sample as indicated by the differential scanning calorimetry (DSC) investigations. The pore size and bulk density of the dried sponge was found to increase from 100 to 500 µm and decrease from 26.7 to 22.4 kg/m, respectively, with an increase in freezing temperature from −70 to −20°C. The drying study at different temperatures reveals that the effective diffusivity of moisture in foam increases from 7.5396 × 10 to 9.8285 × 10 m/s with an increase in drying temperature from 40 to 60°C during the desorption stage. The sponge prepared from gelatin can be utilized as a promising matrix for wound healing and other surgical applications.
... Chitosan is a polymer obtained from the shells of crustaceans which is highly biocompatible and biodegradable (Foda et al., 2007;Lee et al., 2009;Jayakumar et al., 2011). The bacteriostatic and fungistatic properties of chitosan are particularly useful in the wound care management (Sun and Li, 2011). ...
... These fibers bond with wound exudate to form a clear gel that locks-in fluid and absorbs pathogens. The absorbent properties of KytoCel enable it to bind and lock away commonly encountered wound pathogens such as Escherichia coli, Staphylococcus aureus, Candida albicans and MRSA, thereby reducing wound bioburden and the risk of cross-contamination at dressing change (Li et al., 1992;Khor and Lim, 2003;Foda et al., 2007). ...
Article
Full-text available
Wound healing in patients with diabetic foot ulcer differs among people. The wound healing process was influenced by factors like nature of the wound, tissue and an immunity of a person. Any measure taken to control bacterial colonies in wound plays a significant role in wound healing. However, recent emergence of Methicillin-resistant Staphylococcus Aureus (MRSA) associated with chronic wounds created health concerns worldwide. An MRSA colony present in diabetic wounds vulnerable to prolong the wound healing has reported worldwide. Since MRSA are resistant to a wide range of antibiotics, choosing appropriate dressings to treat MRSA colonized wounds has become a challenge. Either synthetic or natural antimicrobial agents are used to develop dressings that combat against MRSA infections. In today’s practice, the incidence of chronic wounds and its associated socioeconomic consequences is rising despite effort and advances in wound management. In this review, an attempt made to summarize various antimicrobial dressings based on its activity against MRSA.
... Subcutaneous implants of these formulations in rats showed reasonable analgesic effect that could be maintained for more than 8 h. Furthermore, the polyelectrolyte complex between chitosan and gelatin produced sponges with improved mechanical properties compared to sponges containing chitosan alone [10]. ...
... .(10). Morphology of chitosan-dextran sulfate (CS-DS) hydrogel by emission scanning electron microscopy field. ...
Article
Full-text available
The purpose of this review is to discuss and summarize some of the interesting findings and applications of modified chitosan (MCS) and their derivatives in different areas of drug delivery. This review highlights the important applications of MCS in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their uses as recipients in drug formulation are also discussed. This review also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting MCS in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized.
... In addition, it should be as low as possible with the consideration to achieve optimum values of desired properties of sponge. The biodegradable polymers currently used as sponge and scaffolds for similar purposes include chitosan, [17] chitosan-gelatin, [18,19] chitosan-alginate, [20] chitin, [21,22] collagen, [23,24] arabinogalactan, [25] alginate, [26] polyglycolide, polylactide and their copolymers, [27,28] hyaluronate, [22,29] and gelatin. [30] Porous biopolymers such as sponge based on naturally occurring biodegradable material can provide a frame to absorb wound fluid and promote healing. ...
... In addition to wound treatment, sponges may also serve as drug carriers. [18,31] Biopolymer used as wound dressings, hemostats, and scaffolds for tissue engineering in the forms of sponges are usually required to disappear by resorption into the body after accomplishment of tissue regeneration within a couple of weeks. [32] The foam may be produced by beating or otherwise mechanically agitating the material to cause the gelatin solution to foam. ...
Conference Paper
Full-text available
Absorbable gelatin foam, commonly used in the surgery to stanch the flow of blood from a wound on the parenchymal organs, was synthesized and dried using freeze dryer (FD) and heat pump dryer (HPD). It was observed that heat pump drying takes 15 % lower time as compared to freeze drying at 38 °C for 2 cm thick foam patch. Freeze dried foam was found to be superior in quality in terms of water intake rate, water holding capacity, pliability, softness, and the pore size distribution. Beside quality aspects, the operating cost in freeze drying is almost 4.5 times higher as against the heat pump drying. Also, the equipment cost for freeze drying is 6 times expensive as compared to heat pump dryer.
... The objective was to prepare BH buccal sponges that have good mucoadhesion force, sustain the mucoadhesion, and have maximum release extent with a suitable release rate. Once prepared, sponges were stored in a dessicator at 65% relative humidity (provided by saturated sodium nitrite solution) and at room temperature to obtain soft pliable sponges before further investigation (18). ...
... The cylindrical plastic molds were frozen at −20°C for 24 h and then freeze-dried at −45°C under a vacuum of 7×10 −2 mBAR. The prepared sponges were stored in a desiccator under the previously mentioned conditions until further investigations (18). The composition of the prepared BH cup and core buccal chitosan sponge was listed in Table I. ...
Article
This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 3(2) factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.
... PECs are obtained by mixing aqueous solutions of two polymers carrying opposite charges 17 . Being cationic polymer, chitosan could interact with anionic polymers as sodium alginate 16,18 , pectin 15,19 , carboxymethyl cellulose sodium (Na CMC) 20 , acacia 21 , polyacrylate 22 , carrageenan 23,24 , hyaluronate 25,26 and gelatin 27,28 . Preparation and evaluation of periodontal films incorporating tetracycline HCl (Tc), based on PECs between chitosan and either sodium alginate or pectin are the topics of this work. ...
Article
Abstract Local intra-pocket drug delivery devices can provide an effective concentration of the antimicrobial agent at the site of action with avoidance of undesirable side effects. This study explored the application of chitosan-alginate and chitosan-pectin polyelectrolyte complex (PEC) films as drug release regulators for tetracycline HCl (Tc) to treat periodontal pockets. Periodontal films with 1:1 Tc:PEC ratio were prepared using 1:1 chitosan (Ch) to sodium alginate (A) or 1:3 Ch to pectin (P). The scanning electron microscope showed acceptable film appearance and differential scanning calorimetry analysis confirmed complex formation. The in vitro release studies for both films showed a burst drug release, followed by prolonged release for 70 h. A prolonged antibacterial activity of both films against Staphylococcus aureus ATCC 6538 was observed over a period of 21 days. Aging studies indicated that the five months storage period in freezer did not significantly influence the drug release profile or the antibacterial activity of both films. Clinical evaluation showed a significant reduction in pocket depth (p < 0.0001) to their normal values (≤3 mm). PEC films could be exploited as a prolonged drug release devices for treatment of periodontal pockets.
... At the end, several examples of applications for drug delivery are mentioned [265,[293][294][295][296]. Chitosan may be processed more easily than chitin to different forms: in sponge, capsule or nanoparticle depending on the tested system and the goal of its administration. ...
Article
Full-text available
This review describes the most common methods for recovery of chitin from marine organisms. In depth, both enzymatic and chemical treatments for the step of deproteinization are compared, as well as different conditions for demineralization. The conditions of chitosan preparation are also discussed, since they significantly impact the synthesis of chitosan with varying degree of acetylation (DA) and molecular weight (MW). In addition, the main characterization techniques applied for chitin and chitosan are recalled, pointing out the role of their solubility in relation with the chemical structure (mainly the acetyl group distribution along the backbone). Biological activities are also presented, such as: antibacterial, antifungal, antitumor and antioxidant. Interestingly, the relationship between chemical structure and biological activity is demonstrated for chitosan molecules with different DA and MW and homogeneous distribution of acetyl groups for the first time. In the end, several selected pharmaceutical and biomedical applications are presented, in which chitin and chitosan are recognized as new biomaterials taking advantage of their biocompatibility and biodegradability.
... Mao and colleagues had developed chitosan-gelatin hybrid polymer network as a pH sensitive matrix for drug delivery [405,406] and later on explored their use in tissue engineering [407][408][409]. The complexes of chitosan-gelatin are not only restricted to delivery of drugs any more [410][411][412] but extended to the DNA delivery [413] and macromolecules as recombinant human bone morphogenetic protein-2 [414]. The chitosan/protein complexes can intensify cytocompatibility via shielding the positively charged chitosan to a suitable charge density, enhance cell proliferation and decline cell apoptosis [415]. ...
Chapter
The nanocomposites are multiphase materials or hybrids in which at least one of the components has dimension in the nanometer scale. These materials exhibit extraordinary mechanical and physical properties than the cocstituent phases. The composites can be tailored to meet the requirements of a particular application with manipulations of these properties. For biomedical applications the polymer composites are of value. Chitoasn is a much appreciated polymer in this respect because of its biocompatbility, biodegrability, nontoxicity and cationic nature. The composites of chitosan can be elaborated with inorganic materials as well as with polyionic materials with polyelectrolyte complex formation. The comopites with calcium phosphate based materials, clays are evaluated for tissue engeneering applications along with their drug eluting properties. The composites of chitosan with metal oxide nanoparticles, metal nanoparticles, carbon nanotubes are maneuvered as biosensors. Similar operations can be developed with chitosan/quantum dots composites in addition to the bioimaging functions. The plethora of biomedical applications is put forword by chitosan/polyion complexes. The future potential of chitosan composites in biomedical applications is very promising for therapeutics and diagnosis. The awareness and the emergence of the analytical protocols for quality assessment of chitosan will see to these applications without delay.
... Furthermore, the polyelectrolyte complex between chitosan and gelatin produced sponges with improved mechanical properties compared to sponges containing chitosan alone. 10 Chitosan-γ-poly (glutamic acid) (see Fig. 7.7) polyelectrolyte complex nanoparticles were investigated as drug carriers for targeted drug delivery, it was shown that they can penetrate A2780/AD ovarian cancer cells and this penetration was significantly faster and more efficient in the presence of conjugated folic acid due to over expression of folate receptors on these cells. 11 Maleic starch half-ester acid is an anionic derivative of starch that produces a polyelectrolyte complex when combined with the polycation, chitosan. ...
Chapter
Full-text available
The purpose of this review is to discuss and summarize some of the interesting findings and applications of modified chitosan (MCS) and their derivatives in different areas of drug delivery. This review highlights the important applications of MCS in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their uses as recipients in drug formulation are also discussed. This review also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting MCS in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized. © 2013 by World Scientific Publishing Co. Pte. Ltd. All rights reserved.
... Chitosan's positive charge allows it to have many electrostatic interactions with negatively charged molecules. Chitosan has many physicochemical (reactive OH and NH 2 groups) and biological (biocompatible, biodegradable) properties that make it an attractive material for use in various applications (Khor and Lim, 2003;Foda et al., 2007). These properties include: Biodegradability, lack of toxicity, anti-fungal effects, wound healing acceleration and immune system stimulation (Prabaharan and Mano, 2005). ...
Article
Full-text available
The adsorption of the Ibuprofen (Ibu) drug on β-cyclodextrin (β- CD) grafted chitosan polymer was studied under different experimental conditions. The effect of Ibu concentration, mass of β-CD grafted chitosan polymer as adsorbent, contact time, temperature and pH were investigated. Three equilibrium models, Langmuier, Freundlich and Temkin isotherm models were analyzed to evaluate the adsorption isotherms. The adsorption isotherms were best fitted by Freundlich isotherm model, with correlation coefficient 0.9882, the intensity of adsorption parameters was lower than one and Freundlich adsorption isotherm constant value was more than one. High adsorption was found in acidic media pH 2, 27°C and 1 h adsorption time. In order to investigate the kinetic of the adsorption process four kinetic models were analyzed, pseudo first order kinetic model, pseudo second order kinetic model, the Elovich kinetic model and intraparticle diffusion kinetic model. Kinetic parameters include; binding strength constant, first order adsorption rate constant, intraparticle diffusion rate constant, adsorption half time, rate constant, equilibrium constant and adsorption capacities. Correlation coefficient for each kinetic equation was reported. The adsorption kinetics was best fitted by pseudo-first order kinetic equation, with correlation coefficient 0.9922. The rate determining step is well described by intraparticle diffusion process. The Intraparticle diffusion rate constant values ranging from 0.163 to 1.1441 mgg−1 min−1/2.
... Subcutaneous implants of these formulations in rats showed reasonable analgesic effect that could be maintained for more than 8 h. Furthermore, the polyelectrolyte complex between chitosan and gelatine produced sponges with improved mechanical properties compared to sponges containing chitosan alone [51]. ...
Article
Full-text available
Chitosan has been the subject of interest for its use as a polymeric drug carrier material in dosage form design due to its appealing properties such as biocompatibility, biodegradability, low toxicity and relatively low production cost from abundant natural sources. However, one drawback of using this natural polysaccharide in modified release dosage forms for oral administration is its fast dissolution rate in the stomach. Since chitosan is positively charged at low pH values (below its pK(a) value), it spontaneously associates with negatively charged polyions in solution to form polyelectrolyte complexes. These chitosan based polyelectrolyte complexes exhibit favourable physicochemical properties with preservation of chitosan's biocompatible characteristics. These complexes are therefore good candidate excipient materials for the design of different types of dosage forms. It is the aim of this review to describe complexation of chitosan with selected natural and synthetic polyanions and to indicate some of the factors that influence the formation and stability of these polyelectrolyte complexes. Furthermore, recent investigations into the use of these complexes as excipients in drug delivery systems such as nano- and microparticles, beads, fibers, sponges and matrix type tablets are briefly described.
... Mao and colleagues had developed chitosan-gelatin hybrid polymer network as a pH sensitive matrix for drug delivery [405,406] and later on explored their use in tissue engineering [407][408][409]. The complexes of chitosan-gelatin are not only restricted to delivery of drugs any more [410][411][412] but extended to the DNA delivery [413] and macromolecules as recombinant human bone morphogenetic protein-2 [414]. The chitosan/protein complexes can intensify cytocompatibility via shielding the positively charged chitosan to a suitable charge density, enhance cell proliferation and decline cell apoptosis [415]. ...
Article
The nanocomposites are multiphase materials or hybrids in which at least one of the components has dimension in the nanometer scale. These materials exhibit extraordinary mechanical and physical properties than the cocstituent phases. The composites can be tailored to meet the requirements of a particular application with manipulations of these properties. For biomedical applications the polymer composites are of value. Chitoasn is a much appreciated polymer in this respect because of its biocompatbility, biodegrability, nontoxicity and cationic nature. The composites of chitosan can be elaborated with inorganic materials as well as with polyionic materials with polyelectrolyte complex formation. The comopites with calcium phosphate based materials, clays are evaluated for tissue engeneering applications along with their drug eluting properties. The composites of chitosan with metal oxide nanoparticles, metal nanoparticles, carbon nanotubes are maneuvered as biosensors. Similar operations can be developed with chitosan/quantum dots composites in addition to the bioimaging functions. The plethora of biomedical applications is put forword by chitosan/polyion complexes. The future potential of chitosan composites in biomedical applications is very promising for therapeutics and diagnosis. The awareness and the emergence of the analytical protocols for quality assessment of chitosan will see to these applications without delay.
... difference in water absorption capacity between the blank and the composite films. This could be due to hydrophilic and swelling properties of gelatin [38,39]. The parameters of tensile strength of the films are given in Table 2. ...
Article
Full-text available
This paper is a part of research aiming at preparing biodegradable films containing gelatin and Carica papaya extract for wound healing purposes in rats. Carica papaya leaves were collected and extracted using methanol aqueous method (20% methanol: 80% water). Eleven films (F1-F11) of Carica papaya extract (0-500) and gelatin (1000 mg) were prepared and investigated for selected in vitro parameters which include pH, thickness, folding endurance, water absorption capacity, tensile strength and extract released studies. Increasing concentrations of the added Carica papaya extract dropped the pH value from 7.3 ± 0.1 to 5.2 ± 0.1. Blank gelatin film had the highest value of the thickness (22.8 ± 0.9 μm). Folding endurance increased significantly (p<0.05) in both blank and composite films. In blank films the values of the folding endurance increased from 122.7 ± 3.5 - 187.6 ± 3.5 while in composite ones the values increased from 232.0 ± 8.8 to 258.3±2.5. Tensile strength value increased with increasing the addition of Carica papaya extract significantly (p<0.05) from 100.4 ± 3.4 N/cm2 to 191.5 ± 3.6 N/cm2. In contrast, within the composite films the highest addition of Carica papaya decreased the tensile strength value significantly (p<0.05) from 332.8 ± 2.2 to 84.10 ± 6.1 N/cm2. Significant differences (p<0.05) were noticed in the values of extract release. The maximum percentage of extract release was 96.6% which was scored in formulation 7 of the films (F7) while the minimum percentage of the extract release was 69.8% which was recorded in formulation 9 of the films (F9). In conclusion, the films contained high concentrations of Carica papaya extract gave promising in vitro results and are recommended to be used for wound healing applications.
... All chitosan's properties are due to its chemical groups (amino and hydroxyl). Biodegradability, absorption and solubility rates are characteristics given by the amino groups, thus transforming chitosan into an appealing option for tissue engineering [60,61]. An advantage of this natural polymer is its high molecular weight, making it a strong viscosity agent and allowing it to act as a pseudoplastic biomaterial in an acid medium [62]. ...
Article
Full-text available
The advancements made in biomaterials have an important impact on oral tissue engineering, especially on the bone regeneration process. Currently known as the gold standard in bone regeneration, grafting procedures can sometimes be successfully replaced by a biomaterial scaffold with proper characteristics. Whether natural or synthetic polymers, biomaterials can serve as potential scaffolds with major influences on cell adhesion, proliferation and differentiation. Continuous research has enabled the development of scaffolds that can be specifically designed to replace the targeted tissue through changes in their surface characteristics and the addition of growth factors and biomolecules. The progress in tissue engineering is incontestable and research shows promising contributions to the further development of this field. The present review aims to outline the progress in oral tissue engineering, the advantages of biomaterial scaffolds, their direct implication in the osteogenic process and future research directions.
... Although, the interest area of many researchers is the modification of Tr release [10][11][12], the organization of its sustained delivery to the oral route has not been well planned, yet. From global health care, patient compliance, perspective and financial, it is necessary to find a novel methodology for oral administration of Tr with well therapeutic efficacy. ...
Article
In comparison with the intravenous route, oral administration is most commonly used owing to the non-invasive nature and the fact that avoids patient pain and discomfort. In this context, UiO-66 was prepared through solvothermal route to load tramadol (Tr) as a model drug. Tr loaded UiO-66 (Tr@UiO-66) was used to improve the drug release controllability of bio-polymeric k-Carrageenan (k-Cr) hydrogel in the gastrointestinal tract (GIT) conditions. The k-Cr/Tr@UiO-66 bio-nanocomposite hydrogel beads were characterized by FT-IR, XRD, EDX, pHpzc, and SEM methods. The in-vitro drug release and kinetics analysis revealed that the k-Cr/Tr@UiO-66 has a better performance against stomach pH and enhanced the drug dosing stability with controlled releases in the GIT conditions. Cytotoxicity study established that the bio-nanocomposite beads have a cytocompatible nature against human colon cells. Results showed that the prepared novel k-Cr/Tr@UiO-66 could be potentially used as a nontoxic oral delivery vehicle.
... To date, chitosan (CS)-based pulmonary delivery systems were extensively used to enhance the permeation and bioavailability of many drugs (19)(20)(21)(22). Crosslinking agents like tripolyphosphate (TPP) or glutaraldehyde (GA) have been widely applied to fabricate sustained release systems (19)(20)(21)(22)(23)(24). However, valid concerns of toxic effects of glutaraldehyde exposure including respiratory epithelium hyperplasia, chronic bronchitis, respiratory tract sensitization that extend to asthma, nasal lesions, skin and eye irritation, headache, fatigue, vomiting, colitis, tachycardia, and fever have been reported (25,26). ...
Article
Full-text available
Risedronate sodium (RS) is a potent inhibitor of bone resorption, having an extreme poor permeability and limited oral bioavailability (0.62%). RS should be orally administered under fasting conditions while keeping in an upright posture for at least 30 min to diminish common gastroesophageal injuries. To surmount such limitations, novel risedronate–chitosan (RS–CS) crosslinker-free nebulizable microspheres were developed adopting the quality by design (QbD) approach and risk assessment (RA) thinking. RS:CS ratio, surfactant (Pluronic® F127) concentration, homogenization duration, speed, and temperature were identified using Ishikawa diagrams as the highest formulation and process risk factors affecting the critical quality attributes (CQAs), average particle size (PS), and entrapment efficiency (EE%). The risk factors were screened using the Plackett–Burman design, and the levels of the most significant factors were optimized using a multilevel factorial design to explore the optimized system with the least PS, maximum EE%, and a prolonged drug release profile. The optimized system (B6) was developed at a RS:CS ratio of 1:7, a surfactant concentration of 2% (w/v), and a homogenization speed of 14,000 rpm. It revealed good correlation with QbD theoretical prediction, where positively charged (47.9 ± 3.39 mV) discrete, spherical microspheres (3.47 ± 0.16 μm) having a high EE% (94.58 ± 0.19%) and prolonged RS release over 12 h (Q12 h, 89.70 ± 0.64%) were achieved. In vivo lung deposition after intratracheal instillation of B6 confirmed the delivery of high RS percentage to rat lung tissues (87 ± 3.54%) and its persistence for 24 h. This investigation demonstrated the effectiveness of QbD philosophy in developing RS–CS crosslinker-free nebulizable microspheres.
... Therefore, a formula avoiding the first-pass effect can be advantageous. Although modification of tramadol release has been the area of interest of many researchers [6][7][8] , yet, shifting its delivery to the buccal route has not been well studied. From a financial, global health care and patient compliance perspective, finding various alternatives to parenteral administration with better therapeutic efficacy is necessary. ...
Article
Full-text available
Treatment of chronic pain is complicated by the evidence that abuse of prescription opioids is rising; therefore, in many cases, chronic pain remains undertreated. Tramadol is an atypical central analgesic with a mixed mechanism of action offering many advantages over conventional opioids. We exploited the nonopioid action of tramadol, by bypassing the first-pass effect, as well as multiparticulate drug delivery. Our aim was to identify optimal formulation parameters for designing polyvinyl alcohol (PVA), single and mixed dual cross-linked tramadol microspheres-loaded hydrogel with adequate bioadhesion and providing controlled drug release for buccal delivery. Microspheres characterization was done by scanning electron microscopy and infrared spectroscopy. Other investigations comprised the evaluation of yield, drug content, particle size, rheology, swelling, mucoadhesion, release, and permeation studies through biological membranes all together with testing the antinociceptive activity and its attenuation by the antagonist naloxone HCl. PVA-alginate microspheres (F3)-loaded carbopol hydrogel attained: the highest mucoadhesion time (1436.67 min ± 5.77) and mucin adsorption capacity, shear thinning thixotropic properties with adequate yield value and hysteresis area, best drug release (RE = 84.20 ± 2.07%) and permeation efficiency (PE = 65.30 ± 7.02%). Dissolution and permeation profiles were compared using similarity factor; F3-loaded carbogel had the lowest value. During in vivo study, the nonsignificant difference between the AUC of the groups receiving F3-loaded carbogel buccally with (group 5) and without (group 4) administration of naloxone, and between group 4 and the oral group, showed that the buccal route may arguably provide an alternative safer route of tramadol administration.
... Wound-dressing materials and tissue engineering are important domains under development [194][195][196][197][198][199][200]. New adhesives were proposed recently [201,202]. ...
Article
In this chapter, the characterization and main properties of chitin and chitosan are described to indicate the advantage of such polysaccharides. The main development in the field of materials concerns chitosan, which is solubilized in acidic conditions whereas chitin is difficult to transform.Chitin is a semi-crystalline polysaccharide that can be processed as fibres or membranes with good mechanical properties due to the cooperative hydrogen bond network formed in the solid state. It has some hydrophilic characteristics and antimicrobial properties. It is also used in composite materials as fibres to reinforce synthetic or natural polymers.Chitosan is more developed due to its solubility in acidic media; it is easy to process under different conformation: fibre, film, sponge, bead and so on. It may be blended with other polymers, especially in electrostatic complexes with alginate or hyaluronan.Numerous application domains are described for these chitin / chitosan-based materials in the literature but mainly in biomedical, pharmaceutical, cosmetics and packaging. The important attributes of these natural polymers are mainly their biocompatibility, antimicrobial properties and biodegradability / resorbability in the body. Another advantage of chitosan is that specific derivatives may be prepared due to the presence of free reactive -NH2 groups on the C-2 position of the D-glucosamine unit.
... Flexible devices with spongy, plastic, or rubbery consistency have numerous applications in drug delivery and tissue engineering. Current biomaterials used for fabricating flexible devices include hydroxyapatite cement [1,2], silicone [3,4], collagen [5][6][7][8], gelatin sponges [9,10], and their combination with synthetic or natural polymers such as elastin [11,12], chitosan [13,14], and polytetrafluoroethylene [15][16][17][18]. ...
Article
The purpose of this research is to design and characterize flexible PLGA-based implants for the controlled release of ciprofloxacin hydrochloride for up to 6 weeks in vitro. This research uses a reversed phase separation/coacervation method to fabricate flexible PLA and PLGA: excipient implants with dichloromethane/mineral oil as solvent/non-solvent. Physical characterization was performed using thermal and mechanical analyses. Drug loading and release studies were performed with ciprofloxacin HCl as the model drug. Release kinetics was modeled to elucidate possible mechanisms of drug release. Four polymer-excipient combinations with glass transition temperatures less than 20°C and representing a wide range of Young's moduli were shown to entrap up to 8% of ciprofloxacin HCl that could be released at a controlled rate for 65 days in vitro. The release rate could consistently fit a ternary Gaussian pattern with an R(2)>0.99. It was postulated that these release patterns could be related to ciprofloxacin that was loosely or poorly bound (burst release), trapped within the polymer matrix, or encapsulated by the polymer. These studies show that flexible implants can be fabricated from PLGA-based polymers for the controlled release of ciprofloxacin hydrochloride for up to 6 weeks in vitro.
... An additional use for chitosan in orthopedics includes a direct replacement of bone or hard tissue. It is also a natural bioadhesive used to improve bone cement which is used to secure implants as well as to fill bone cavities (Foda, El-Laithy, & Tadros, 2007;Khor & Lim, 2003;Senel & McClure, 2004). ...
Chapter
Full-text available
Biomaterials have been used increasingly in various fields, such as drug delivery, imaging, and tissue engineering. The main reason justifying the widespread use of biomaterials relies on its valuable and low-cost source of new drugs. Current research goals are focused on identifying more potent and specific compounds with antitumor, immunomodulatory, antihyperlipidemic, anticoagulant, and antiviral activities. The increasing knowledge of structural analysis and chemical modifications enables the use of these marine carbohydrates in a newer way for the human welfare. This chapter focuses on the recent developments related to industrial and biomedical applications using chitin, chitosan, alginate, agar, and carrageenan derivatives and reports the main advances published over the last 10-15 years.
Article
Chitosan-gelatin polyelectrolyte complexes were fabricated and evaluated as tissue engineering scaffolds for cartilage regeneration in vitro and in vivo. The crosslinker for the gelatin component was selected among glutaraldehyde, bisepoxy, and a water-soluble carbodiimide (WSC) based upon the proliferation of chondrocytes on the crosslinked gelatin. WSC was found to be the most suitable crosslinker. Complex scaffolds made from chitosan and gelatin with a component ratio equal to one possessed the proper degradation rate and mechanical stability in vitro. Chondrocytes were able to proliferate well and secrete abundant extracellular matrix in the chitosan-gelatin (1:1) complex scaffolds crosslinked by WSC (C1G1WSC) compared to the non-crosslinked scaffolds. Implantation of chondrocytes-seeded scaffolds in the defects of rabbit articular cartilage confirmed that C1G1WSC promoted the cartilage regeneration. The neotissue formed the histological feature of tide line and lacunae in 6.5months. The amount of glycosaminoglycans in C1G1WSC constructs (0.187±0.095μg/mg tissue) harvested from the animals after 6.5months was 14wt.% of that in normal cartilage (1.329±0.660μg/mg tissue). The average compressive modulus of regenerated tissue at 6.5months was about 0.539MPa, which approached to that of normal cartilage (0.735MPa), while that in the blank control (3.881MPa) was much higher and typical for fibrous tissue. Type II collagen expression in C1G1WSC constructs was similarly intense as that in the normal hyaline cartilage. According to the above results, the use of C1G1WSC scaffolds may enhance the cartilage regeneration in vitro and in vivo.
Article
Frequent instillation of terbinafine hydrochloride (T HCl) eye drops (0.25%, w/v) is necessary to maintain effective aqueous humor concentrations for treatment of fungal keratitis. The current approach aimed at developing potential positively charged controlled-release polymeric nanoparticles (NPs) of T HCl. The estimation of the drug pharmacokinetics in the aqueous humor following ocular instillation of the best-achieved NPs in rabbits was another goal. Eighteen drug-loaded (0.50%, w/v) formulae were fabricated by the nanopreciptation method using Eudragit® RS100 and chitosan (0.25%, 0.5%, and 1%, w/v). Soybean lecithin (1%, w/v) and Pluronic® F68 (0.5%, 1%, and 1.5%, w/v) were incorporated in the alcoholic and aqueous phases, respectively. The NPs were evaluated for particle size, zeta potential, entrapment efficiency percentage (EE%), morphological examination, drug release in simulated tear fluid (pH 7.4), Fourier-transform IR (FT-IR), X-ray diffraction (XRD), physical stability (2 months, 4°C and 25°C), and drug pharmacokinetics in the rabbit aqueous humor relative to an oily drug solution. Spherical, discrete NPs were successfully developed with mean particle size and zeta potential ranging from 73.29 to 320.15 nm and +20.51 to +40.32 mV, respectively. Higher EE% were achieved with Eudragit® RS100-based NPs. The duration of drug release was extended to more than 8 h. FT-IR and XRD revealed compatibility between inactive formulation ingredients and T HCl and permanence of the latter's crystallinity, respectively. The NPs were physically stable, for at least 2 months, when refrigerated. F5-NP suspension significantly (P < 0.05) increased drug mean residence time and improved its ocular bioavailability; 1.657-fold.
Article
Full-text available
The objectives of study were the development of new formulations of Tramadol HCl (TmH) microspheres and their evaluation primarily for kinetics and stability. Microspheres of different polymer concentration M1 (1:1). M2 (1:2) and M1, (1:3) were developed and compressed into tablets i.e.. T1, T2 and T3. respectively Zero order, First order. Higuchi. Hixson-Crowell and korsmeyer-Peppas kinetic models were applied to assess the mechanism and pattern of drug release Higuchi model was found to be the best among all models. The chemical and physical stabilitv of TmH formulation was studied using FTIR. Thermal analysis. X-ray diffraction and dissolution tests. In-vitro analysis showed that tablets of ratio T 2 released the drug over 12hrs and the release profilewas comparable with that of reference tablet. TramalR SR The effect of different storage temperatures on the phvsicochemical stability of T2 was insignificant (p > 0 05).
Article
The purpose of this work was to develop an extended release matrix tablet of nicorandil; a freely water soluble drug used in cardiovascular diseases. Chitosan (CH)/hyaluronate sodium (HA), pectin (PE) or alginate sodium (AL) interpolymer complexes (IPCs) were prepared. The optimum IPCs (CH:HA, 40:60), (CH:PE, 30:70) and (CH:AL, 20:80) were characterized by Fourier transform infrared spectroscopy. The IPCs were based on electrostatic interactions between protonated amine groups of CH and carboxylate groups of HA, PE or AL. Nicorandil matrix tablets were prepared using the optimum IPCs, alone or in combination with Imwitor® 900 K. Evaluations such as weight variation, thickness, content uniformity, friability, disintegration and in vitro release studies were performed. The tablets showed acceptable pharmacotechnical properties and complied with compendial requirements. Results of the dissolution studies revealed that formula F11 (CH:AL, 20:80) IPC:Imwitor® 900 K, 3:1) could extend drug release >8 h. Most formulae exhibited non-Fickian diffusion drug release profiles. When compared to the immediate release Ikorel® tablet, the duration of effective nicorandil therapeutic concentration from formula F11, in healthy human volunteers, was significantly (P < 0.05) extended from 4 to 8 h with expected lowering in side effects potential.
Article
Although most cellular polymers are made from thermoplastics using different foaming technologies, gelatin and many other natural polymers can form hydrogels and convert them to cellular solids using various techniques, many of which differ from traditional plastic foaming, and so does their resulting structures. Cellular solids from natural hydrogels are porous materials that often exhibit a combination of desirable properties, including high specific surface area, biochemical activity, as well as thermal and acoustic insulation properties. Among natural hydrogels, gelatin-based porous materials are widely explored due to their availability, biocompatibility, biodegradability and relatively low cost. In addition, gelatin-based cellular solids have outstanding properties and are currently subject to increasing scientific research due to their potential in many applications, such as biocompatible cellular materials or biofoams to facilitate waste treatment. This article aims at providing a comprehensive review of gelatin cellular solids processing and their processing-properties-structure relationship. The fabrication techniques covered include aerogels production, mechanical foaming, blowing agents use, 3D printing, electrospinning and particle leaching methods. It is hoped that the assessment of their characteristics provides compiled information and guidance for selecting techniques and optimization of processing conditions to control material structure and properties to meet the needs of the finished products.
Article
The current work aimed to develop novel composite sponges of chitosan (CH)-chondroitin sulfate (CS) as a low-density gastroretentive delivery system for lornoxicam (LOR). This triple anti-inflammatory therapy-loaded matrices are expected to expand and float upon contact with gastric fluids for prolonged times. CH and CS solutions (3%, w/w) were prepared, mixed in different ratios, lyophilized, coated with magnesium stearate and compressed. The CH:CS interpolymer complex (IPC) was evaluated via FT-IR, DSC, and XRD. The compressed-sponges were evaluated for appearance, structure, porosity, pore diameter, density, wetting-time, floating characteristics, adhesion-retention, and LOR-release. The gastroretentivity of the best achieved magnetite-loaded sponges was monitored in healthy volunteers via MRI. The interaction between CH (protonated amino groups) and CS (anionic carboxylate/sulfate groups) proved IPC formation. DSC and XRD studies confirmed loss of LOR crystallinity. The sponges possessed interconnecting porous-network structures. The porosity, mean pore diameter, and bulk density of CH:CS (10:3) IPC sponges were 11.779%, 25.4nm, and 0.670g/mL, respectively. They showed complete wetting within seconds, gradual size-expansion within minutes and prolonged adhesion for hours. Controlled LOR-release profiles were tailored over 12h to satisfy individual patient needs. Monitoring of sponges via MRI proved their gastroretentivity for at least 5h.
Article
Abstract The present study was designed to determine the role of curcumin-β-cyclodextrin-loaded sponge on burn wound healing in rats. Curcumin-β-cyclodextrin complex was prepared by the solvent evaporation encapsulation method. Molecular inclusion complex of curcumin-β-cyclodextrin was incorporated into gelatin sponge. The developed sponge was characterized for drug entrapment, drug release and morphology. The biological activity of optimized formulation was determined on burn wounds which were made on rats. The burn wound healing efficacy was analyzed through physical and histological changes observed at the wound sites. There was a significant decrease in rate of wound contraction in experimental groups then the control group. Curcumin-β-cyclodextrin-loaded sponge treated wound was found to heal in rate comparable to marketed formulation with no sign of adverse consequence. The result clearly substantiates the beneficial effects of curcumin-β-cyclodextrin-loaded sponge in the acceleration of wound healing.
Article
Natural polymers are used as lead compounds for design of therapeutic drugs in treatment of different ailments. Chitosan and gelatin have proven wound healing properties individually. As both have wound healing property, the combination of two polymers shown improvement in wound healing property. Thus, the composite films were evaluated for various in vitro and invivo tests to ascertain the applicability of prepared combination for wound healing activity. The composite films were prepared with increase in gelatin concentration and were evaluated for thickness, folding endurance, water absorption capacity, tensile strength and for biological properties like antimicrobial activity and in vivo wound healing performance by excision wound model. With increase in gelatin concentration, thickness, folding endurance, water absorption capacity and tensile strength were increased. Percentage of wound contraction was more in wounds treated with chitosan-gelatin composite film. With the above results, it was concluded that chitosan-gelatin combination has improved wound healing property than chitosan film alone.
Article
This non-comparative study explored the benefits of a natural gelling fibre dressing in 10 children with epidermolysis bullosa (EB). The clinical challenge in managing these children is that they often present with recalcitrant wounds that are perpetuated by critical colonisation, presence of biofilms and infection. KytoCel® (Aspen Medical) is a highly absorbent dressing composed of natural, biodegradable acylated chitosan. These fibres bond with wound exudate to form a clear gel that locks in fluid absorbs pathogens and is conformable to the wound bed. It also has haemostatic properties. ( Dutta PK et al, 2004 ; Lee et al, 2009 ; Stephen Haynes et al, 2014 ). Factors considered were whether the dressing could aid healing, reduce bleeding, reduce bioburden, be atraumatic and comfortable during wear time and removal.
Article
Chitosan (Cs) based biomaterials seem to be indispensable for neovasculogenesis and angiogenesis that ensure accelerated wound healing. Cs/poly (vinyl alcohol) (PVA) bio-constructs were cross-linked and investigated with varying concentrations of aminopropyltriethoxysilane (APTES). This study comprised of three phases: fabrication of hydrogels, characterization, assessment of angiogenic potential along with toxico-pathological effects, wound healing efficacy in chick and mice, respectively. The hydrogels were characterized by FTIR, SEM and TGA and the swelling response was examined in different solvents. The hydrogels swelling ratio was decreased with increasing amount of APTES, showed the highest swelling at acidic and basic pH while low swelling at neutral pH. Chorioallantoic membranes (CAM) assay was performed to study in-vivo angiogenesis, toxicological, morphological, biochemical and histological analyses in developing chicks. The results showed remarkably improved angiogenesis with little deviations in morphological, histological features and liver enzymes of chick embryos at higher concentrations of APTES. Besides, full thickness wounds were excised on mice dorsolateral skin to assess the wound healing. The rate of wound size reduction was significantly higher after topical application of hydrogels with elevated levels of crosslinker. Hence, the hydrogels showed enhanced angiogenesis, accelerated wound healing with little or no observable in-vivo toxicity.
Article
Carvedilol (CVD) suffers from low absolute bioavailability (25%) due to its limited aqueous solubility and hepatic first-pass metabolism. Hydroxypropyl methylcellulose (HPMC) laminated buccal sponges loaded with CVD microemulsions (CVD-ME) were exploited to surmount such limitations. Six pseudoternary-phase diagrams were constructed using Capmul® MCM C8/Capmul® PG8, Tween® 80, propylene glycol and water. Six CVD-ME systems (0.625% w/v) were incorporated into HPMC core sponges backed with Ethocel® layers. The sponges were preliminary evaluated via FT-IR, DSC and XRD. The surface pH, morphology and in vitro drug release studies were evaluated. In vivo mucoadhesion and absorption studies of the best achieved laminated sponges (F4) were assessed in healthy volunteers. CVD-ME systems displayed nano-spherical clear droplets. The sponges showed interconnecting porous matrices through which CVD was dispersed in amorphous state. No intermolecular interaction was detected between CVD and HPMC. The surface pH values were almost neutral. The sponges loaded with CVD-ME systems showed more sustained-release profiles than those loaded with CVD-powder. Compared to Dilatrend® tablets, the significantly (P<0.05) higher bioavailability (1.5 folds), delayed Tmax and prolonged MRT(0-∞) unraveled the dual-potential of F4 sponges for water-insoluble drugs, like CVD, in improving drug oral bioavailability and in controlling drug release kinetics via buccal mucosa.
Article
Chitin and chitosan are amino polysaccharides having multidimensional properties, such as biocompatibility, biodegradability, antibacterial properties and non-toxicity, muco-adhesivity, adsorption properties, etc., and thus they can be widely used in variety of areas. Although human history mainly relies on the biopolymers, however synthetic materials like polyvinyl alcohol (PVA) have good mechanical, chemical and physical properties. Functionalization of PVA with chitin and chitosan is considered very appropriate for the development of well-designed biomaterials such as biodegradable films, for membrane separation, for tissue engineering, for food packaging, for wound healing and dressing, hydro gels formation, gels formation, etc. Considering versatile properties of the chitin and chitosan, and wide industrial and biomedical applications of PVA, this review sheds a light on chitin and chitosan based PVA materials with their potential applications especially focusing the bio-medical field. All the technical scientific issues have been addressed highlighting the recent advancement.
Article
Full-text available
Present investigation was aimed to develop Zaltoprofen-loaded extended-release (ER) pellets formulation for prolonged release. The matrix type of pellets was prepared by extrusion-spheronization technique using calcium chloride-mediated gelatin–κ-carrageenan (G–κ-Carr) polyelectrolyte complex (PEC) hydrogel using rotatable central composite design. The pellets were characterized for physicochemical, morphological, solid-state characterization and flow properties. The formulations were also estimated for drug release and mucoadhesion potential. The optimized formulation (F1) containing 5:5 ratio of G–κ-Carr showed a drug release up to 98.2% and mucoadhesion of 95%. Optimized formulation showed acceptable release pattern, and hence would be viable alternative to ER type of formulations.
Chapter
Nanomedicine employs biofabrication tools to overcome the challenges raised during the delivery of vaccines, material implants, disease diagnosis, and tissue engineering devices, and it also aids in the manipulation of materials with unusual properties of strength, hardness, reduced friction, and increased biocompatibility. This chapter reviews the special features offered by chitosan biopolymer and its derivatives that can be exploited for the fabrication of biomedical probes and for the advancement of nanomedicine. It presents the opportunities to broaden the uses of chitosan toward the advancement of nanomedicine for biofabrication. Chitosan using layer-by-layer (LBL) assembly allowed for the fabrication of multilayer thin films with altered optical, mechanical, and conductive properties as well as hybrid films, which can be applied in biosensing, enzymatic hydrolysis, metal ion detection, protein immobilization, and anticoagulation purposes. Chitosan with superior antibacterial activity and suitability for controlled drug release applications was obtained when manufactured in the form of nanosize particles or vesicles.
Article
The current work aimed to develop low-density gastroretentive sponges loaded with alfuzosin HCl (ALF) to sustain the rate of drug release, improve its oral bioavailability and deliver it to the main site of absorption. Sponges were developed, according to a 2³ full factorial design, by compression of the lyophilized ALF-loaded hydroxypropylmethylcellulose (HPMC) or chitosan (CH) solutions. The influences of the polymer type, grade and concentration on the appearance, topography, porosity, density, in-vitro ALF release, floating behavior, swelling, erosion, and mucoadhesive potential of the developed sponges were explored. Based on the desirability value, the best achieved system was selected. The gastroretentive potential of this system was evaluated in healthy male volunteers via MRI. Soft and flexible sponges were developed. They were characterized with interconnecting pores and channels and had excellent floating properties with respect to floating lag time and duration. Compared to HPMC-based sponges, CH-based ones exhibited higher porosity, larger pore diameters, lower bulk densities, higher drug release rates, larger swelling ratios, faster erosion rates and better mucoadhesive properties. MRI of magnetite-loaded best-achieved CH-based system (F8) ascertained the development of a promising gastroretentive system; exhibiting a gastric residence period of at least 5 h.
Chapter
Chitosan is a unique, naturally obtained polysaccharide derived from chitin. As a biomaterial, it attains immense interest for tissue engineering due to its biocompatibility and biodegradation which also exhibits desired properties such as bactericidal, fungicidal, and enhanced immune activity. Chitosan-based materials are mainly focused on fabricating scaffolds for tissue engineering. The ideal features of scaffolds are three-dimensional, highly porous, biocompatible, and bioresorbable, with cell attachment, proliferation, and implantation. Especially, these scaffolds have distinctive advantages, such as preservation of cellular binding and bioactive factor enrichment. This chapter highlights chitosan-based scaffolds and its composites having higher potential to be employed in bone, cartilage, liver, nerve, and musculoskeletal tissue engineering.
Article
Due to the advantages of non-invasiveness and painlessness, oral administration can be applied to deliver opioid analgesics to interfere with chronic pain. However, the variability of pH in the gastrointestinal environment brings huge challenges for drug delivery. In order to establish an oral delivery vehicle that can controllably exist in the gastrointestinal environment. Tramadol (Tr) was selected as a model drug and the composite drug-loaded hydrogel based on sodium alginate and chitosan was synthesized by a simple cross-linking method. FT-IR, XRD, FESEM and other characterization methods have proved the formation of composite gel networks, which is caused by the strong interaction of functional groups between polysaccharides. Swelling and in-vitro release experiments also show that the composite Tr-loaded gel exhibits a relatively stable swelling and release behavior (about 73% of the release rate can be stabilized in gastrointestinal delivery process). By adjusting the ratio of alginate and chitosan, the responsive behavior of the hydrogel under different pH conditions can be further controlled. This study shows that alginate/chitosan composite hydrogel has specific pH-responsive characteristics, which provides an effective solution for the design of controllable oral delivery analgesic carriers.
Article
Full-text available
We investigated the water sorption properties of macroporous cryogels of gelatine (Gel) and dextran dialdehyde (DDA) prepared via cryogelation at 260 K and following the freeze drying processes. Water vapour sorption isotherms for aerogels were studied at 293 K by two independent methods: static-gravimetric and dynamic vapour sorption (DVS) over a water activity range of 0.11–1.0. Experimental data were fitted by use of the Brunauer–Emmett–Teller (BET) and Guggenheim–Anderson–de Boer (GAB) models. The BET model (for a water activity range of 0.1 ≤ p/po ≤ 0.5) was used to calculate the sorption parameters of the studied cryogels (the monolayer capacity, surface area and energy of interaction). In comparison with BET, the GAB model can be applied for the whole range of water activities (0.1 ≤ p/po ≤ 0.95). This model gave an almost perfect correlation between the experimental and calculated sorption isotherms using nonlinear least squares fitting (NLSF). Confocal Laser Scanning Microscopy (CLSM) was used to confirm the structural differences between various DDA:Gel cryogel compositions. Thermogravimetric analysis and DSC data for aerogels DDA:Gel provided information regarding the bonded water loss, relative remaining water content of the material and the temperature of decomposition. Estimation of the amount of bound water in the cryogels after the freeze drying process as well as after the cycle of treatment of cryogels with high humidity and drying was performed using DSC. The results of the DSC determinations showed that cryogels with higher gelatin content had higher levels of bonded water.
Article
An advanced wound care dressing that uses a natural resource in its ability to absorb and retain moisture as well as to provide antimicrobial properties, offers a new multi-functional, biointeractive protease modulator to the wound dressing arena. Several factors indicate the need for such a dressing, namely: an ageing population inevitably increases the prevalence of wounds managed across acute and community settings, the prevention and management of infection remains a priority and the use of natural resources is becoming more important. This article considers the literature supporting this product and, using care study examples, demonstrates its potential impact on patient outcomes.
Article
Full-text available
Chitosan microspheres containing furosemide were prepared from a w/o emulsion system using liquid paraffin as the external phase and a solution of chitosan in acetic acid as the disperse phase. Discrete spherical furosemide microspheres having a 350–690 μm diameter range were produced. Microsphere properties were affected by the preparation variables such as the type and concentration of chitosan, drug concentration, cross-linking process, the viscosity of oil and stirring rate during the preparation. The results were examined kinetically. Dissolution data indicated that the release followed the Higuchi matrix model.
Article
Full-text available
With an aim of improving bone regeneration, chitosan sponge containing platelet-derived growth factor-BB (PDGF-BB) were developed. For fabrication of chitosan sponge, chitosan solution was freeze-dried, crosslinked and freeze-dried again. PDGF-BB was incorporated into the chitosan sponge by soaking chitosan sponge into the PDGF-BB solution. Release kinetics of PDGF-BB, cell attachment, proliferation capacity and bony regenerative potentials of PDGF-BB-loaded chitosan sponge were investigated. Prepared chitosan sponge retained porous structure with 100 μm pore diameter that was suitable for cellular migration and growth. Release rate of PDGF-BB could be controlled by varying initial loading content of PDGF-BB to obtain optimal therapeutic efficacy. PDGF-BB-loaded chitosan sponge induced significantly high cell attachment and proliferation level, which indicated good cellular adaptability. PDGF-BB-loaded chitosan sponge demonstrated marked increase in new bone formation and rapid calcification. Degradation of the chitosan sponge was proceeded at defect site and subsequently replaced with new bone. Histomorphometric analysis confirmed that PDGF-BB-loaded chitosan sponge significantly induced new bone formation. These results suggested that chitosan sponge and PDGF-BB-loaded chitosan sponge may be beneficial to enhance periodontal bone regeneration.
Article
Full-text available
The analgesic and anti-inflammatory effects of subcutaneously administered bupivacaine, morphine and tramadol on formalin-induced inflammation were compared. 0.25 % bupivacaine in Group B, 20 mg/kg tramadol in Group T, 1 mg/kg morphine in Group M and 0.9 % NaCl in Group S in a volume of 200 micro l were injected into the right hind paw of the rats (n: 40) 15 minutes before injection of 50 micro l 5 % formalin. Sedation and pain behaviour scores, number of flinches and licking-time were recorded. The degree of dermal edema, intraneural edema, vasodilation, erythrodiapedesis, infiltration of polymorphonuclear leukocyte/lymphocyte and mast cell counts were analyzed histopathologically. In Group T and B, circumferential changes were lower than in Group M and S. The pain behaviour scores were significantly lower in Group T and B. The number of flinches in Group T was lower than Group B and S. The vasodilation was significant only in Group M. The dermal edema was limited to deep dermis only in Group T. Preinflammational subcutaneous tramadol infiltration can provide effective analgesia and may have anti-inflammatory effects.
Article
Three types of chitosan films containing prednisolone (PD) were prepared and drug release fromt the films was studied in vitro. The films prepared include 1) a monolayer type (ML) film prepared by evaporating the solvent from a chitosan/drug mixture, 2) a double layer type (DL) film prepared by sticking together two ML films, one of which contained a drug, and 3) N-Ac film which is a DL film with one of the ML films N-acetylated and stuck onto the other ML film, which contained a drug. Release of PD from ML films was retarded as the films became thicker. Release of the drug from N-Ac films was more depresed than from the corresponding DL film and was found to follow zero-order kinetics. Pores were observed in chitosan films by scanning electron microscopy. These result suggested that chitosan and N-acetyl chitosan (chitin) films could be applicable for controlled-release preparations of drugs.
Article
Chitosan, a natural, biocompatible polymer, is becoming popular in dosage form design. In our study the design factors affecting the release of lidocaine and lidocaine chloride from chitosan hydrocolloids and gels were studied. In hydrocolloids a relatively high viscosity was found at low concentrations of chitosan caused by the increased effective volume of the polymer molecules, due to the reflection of the same charges in the chains. The drug release is slow and sustained, being influenced by the chitosan content. The mechanism of chitosan gel formation is not known exactly, but it is clear that for gel formation the length of the chitosan chains and the degree of reacetylation are responsible. The release profile of gels follows almost zero order kinetics. Also, the degree of reacetylation is responsible for the release behaviour. The rotational motion of nitroxides (Tempol, spin-labeled lidocaine) determined by EPR experiments showed practically equal rotational motion at different degrees of reacetylation. Thus, it was concluded that the free spaces, available for nitroxide rotation, were not changed significantly. The degree of reacetylation affects the translational diffusion more strongly.
Article
In this study, chitosan microspheres and sponges were prepared and characterized for diverse biomedical applications successfully. The chitosan microspheres were obtained with a “suspension crosslinking technique” in the size range of 30–700 μm. The stirring rate of the suspension medium and the chitosan/acetic acid ratio, emulsifier, and crosslinker, that is, the glutaraldehyde concentration in the suspension medium, were evaluated as the effective parameters on the size/size distributions of the microspheres. The microsphere size/size distributions were increased with the decreasing of all effective parameters except the chitosan/acetic acid ratio. In the second part of the study, chitosan sponges were prepared with a solvent-evaporation technique and sponges were cross-linked either during the formation or after the formation of sponges by using a cross-linker, that is, glutaraldehyde. When the sponges were crosslinked during the formation, fibrillar structures were obtained, while the leaflet structures were obtained in the case of crosslinking after the formation of sponges. In the last part of the study, the swelling behavior of both the chitosan microspheres and sponges were evaluated using different amounts of the crosslinker. The swelling ratio was increased in both types of structures, that is, microspheres and sponges, by decreasing the amount of the crosslinker. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1637–1643, 2000
Article
Theoretically expected rates of release of solid drugs incorporated into solid matrices have been derived for several model systems. Mathematical relations have been obtained for cases (a) where the drug particles are dispersed in a homogeneous, uniform matrix which acts as the diffusional medium and (b) where the drug particles are incorporated in an essentially granular matrix and released by the leaching action of the penetrating solvent. Release from both planar surface and a sphere is considered. The unidimensional release rates are shown to follow our earlier equation derived for release from ointment bases. Release rates from spherical pellets by both model mechanisms are shown not to follow first-order relationships. The analyses suggest that for the latter system the time required to release 50 per cent of the drug would normally be expected to be approximately 10 per cent of that required to dissolve the last trace of the solid drug phase in the center of the pellet.
Article
Chitosan sponges as sustained release drug carriers were prepared by freeze-drying partially N-acetylated chitosan gels and crosslinked chitosan solutions. Micronized triamcinolone acetonide was used as a model drug. N-acetylchitosan sponges were prepared from 2.5% chitosan solutions acetylated with 10.58 mmol of acetic anhydride per gram of chitosan. Crosslinked chitosan sponges were prepared from 2.5% chitosan solution crosslinked with 1.33% glutaraldehyde in respect to chitosan mass. Drug content in both N-acetylated and crosslinked chitosan sponges were uniform. Scanning electron microscopy (SEM) photos show a leaflet- or a platelet-like structure of both chitosan sponges. The incorporated drug was found in a crystalline form. The water uptake ability of both chitosan sponges was more than 20 times of their weight. The pH of dissolution media and the drug content of the sponges affected the release rate of the drug. The drug release at pH 1.2 was faster than at pH 7.4. The drug release at pH 7.4 was a function of square root of time over 52 h from the N-acetylchitosan sponges and over 36 h from the crosslinked chitosan sponges. With increasing the drug content a slower drug release was found. The delayed drug release was due to the decreased chitosan solubility by either N-acetylation or crosslinking.
Article
In recent years peptides and proteins have received much attention as candidate drugs. For many peptides, particularly hormones, it is desirable to release the drug continuously at a controlled rate over a period of weeks or even months. Polylactic acid and poly(lactic-co-glycolic) acid are well known biocompatible biodegradable materials with wide applications including the design of controlled-release systems for pharmaceutical agents. Polylactic acid implants containing vapreotide were prepared by an extrusion method and drug release was evaluated in vivo in rats using an RIA method The development of an injectable, biodegradable depot formulation of a somatostatin analogue (vapreotide) is described which ensures satisfactory peptide blood level in rats over ∼250 days. A modification of this formulation by means of a wear coating allows minimisation of the initial burst a feature rarely discussed.
Article
Biodegradable implants containing 10 mg of gentamicin each were prepared by compressing the polymer-drug mixture. The liberation of gentamicin from the implants and the biodegradation of the implants were investigated by following in vitro and in vivo experiments. Implants based on pure poly(l-lactic acid) (L-PLA) released the incorporated antibiotic throughout 30 days with a decreasing delivery rate. During the first 24 h L-PLA implants released a total amount of 3600 μg gentamicin. Within 14 days the release rate had decreased to about 12 μg/day. The release profile of implants based on dl-lactic acid-glycolic acid copolymer (RG 502) was completely different. About 1900 μg were released from the copolymer implants during the first 24 h. Release rate decreased to a value of about 3 μg/day 15 days after implantation. In a second phase, starting 20 days after implantation, drug delivery increased again to reach values of about 100 μg/day at the end of the experiment, i.e. 28 days after implantation. Very good tissue compatibility arises from the absence of inflammatory reactions throughout the entire time of implantation as shown by microscopy examinations. The developed implants based on biodegradable polymers are suited for the treatment of acute and chronic bone and tissue infections due to their specific release profiles, their excellent histocompatibility and their biodegradability.
Article
Biodegradable gelatin microspheres containing free methotrexate (MTX) (GMFM) and gelatin microspheres containing MTX covalently conjugated to gelatin using carbodiimide (GMCM-I) and two types of azide coupling-grafting methods (GMCM-II and GMCM-III) have been prepared and evaluated for their efficacy towards the solid tumor fibrosarcoma in Wistar rats. The tumor was induced by inoculation of a 10% tumor cell suspension in the anterior aspect of the hind limb. Seven groups were studied—untreated control, intratumoral (i.t.) injection of free MTX, i.t. injection of placebo microspheres, i.t. injection of GMFM, i.t. injection of GMCM-I, i.t. injection of GMCM-II and i.t. injection of GMCM-III of mean particle size 10–20 μm. The gelatin-microspheres-entrapped MTX showed an improved antitumor activity over free MTX as evidenced by the gross tumor weight assessments and [3H]thymidine incorporation studies in vitro. This was attributed to the slow and controlled release of MTX from gelatin microspheres, which was more effective compared with free MTX given over the same period of treatment. The drug release from microspheres is due to gradual degradation of the spheres and concomitant diffusion of drug into the external medium. GMCM showed higher antitumor activity than GMFM. The antitumor activity of the various GMCM preparations was of the order: GMCM-I > GMCM-II > GMCM-III. The injectable MTX-containing gelatin microspheres can thus be a potential alternative to conventional therapy using free MTX in the treatment of solid tumors such as fibrosarcoma.
Article
The anticancer drug methotrexate (MTX) was covalently linked to gelatin using carbodiimide as the coupling agent. The resulting gelatin-methotrexate conjugate (GMC) was separated by gel filtration and characterised by UV and IR spectroscopy. The drug content of the conjugate was 200 μg MTX/mg gelatin. The GMC was used to prepare biodegradable hydrophilic gelatin microspheres (GMCM) of different mean particle sizes (1–5, 5–10 and 15–20 μm). The in vitro release of MTX from GMCM was investigated in simulated gastric and intestinal fluids. GMCM released MTX in a zero-order manner for 7–9 days in gastric medium and for 8–10 days in intestinal medium. The release data also indicated that the rate of release of MTX decreased with increase in particle size of GMCM. Release of MTX was faster in gastric medium when compared to intestinal medium.
Article
The formation of complex coacervates between the oppositely charged polyions, chitosan and type B gelatin, was investigated. The complex formation was rapid and only observed at very diluted chitosan concentrations over a narrow pH range. The optimum chitosan-gelatin ratio was found to be 1:10 to 1:20, above or below which the coacervate yield decreased significantly. The coacervate yield decreased at higher temperatures and increased ionic strength. Complex coacervation was found to be dependent upon the molecular weight and bloom strength of the polymers. Several model compounds (clofibrate, piroxicam, sulfamethoxazole) were successfully encapsulated within the chitosan-gelatin coacervates.
Article
This review is a survey of studies on protein-stabilized foams and emulsions in relatively simple, well-defined systems (rather than in food products per se). The emphasis is on the extent of basic understanding developed, particularly in terms of the physicochemical properties involved. The stability of the system, its formation, and its rheology are covered. Unfortunately, much work is of limited fundamental value because of poorly designed experimental approaches and the failure to measure key parameters. Reasonable generalization can be made concerning the effects of a number of variables, particularly protein solubility, pH, protein structure and the presence of small molecule surfactants. However, several possible explanations of these effects in terms of surface properties remain tenable. A number of observations can fairly confidently be ascribed to the influence of rheology on flow processes within foams and emulsions.
Article
Chitosan, a hydrophilic biopolymer, is obtained industrially by hydrolysing the aminoacetyl groups of chitin. It is a natural, non-toxic, biodegradable polysaccharide available as solution, flake, fine powder, bead and fibre. The sources, biochemical aspects, structure and chemical modification, physico-chemical and functional properties, and applications of chitosan have been investigated extensively in the literature. In this paper, the attractive properties and broad applications of chitosan-based microparticles, their versatile properties, different preparation methods, and pharmaceutical and biopharmaceutical applications are reviewed.
Article
The influence of acid type used to dissolve chitosan on the resulting sponge physical properties, and their consequent effect on the drug liberation were investigated. Chitosan was dissolved in different acid solutions and chitosan-gelatin sponges were produced by frothing up the polymer solution and then freeze-drying the foam. Prednisolone was used as a model drug. Using tartaric or citric acid resulted in instable, soft, elastic and disintegrating sponges with fast drug release. Elastic but harder sponges from stable foams were obtained when hydrochloric or lactic acid were used. The use of acetic or formic acid enabled the production of stable foams, soft and elastic sponges and a slow drug release. The rate of drug release was decreased by crosslinking the polymers with glutaraldehyde, but only if acetic, formic or acetic acid were used. Therefore, it is possible to manipulate the mechanical properties and the drug liberation rate by using different acids to dissolve chitosan.
Article
We investigated the effects of acute and chronic tramadol treatment on T lymphocyte function and natural killer (NK) cell activity in rats receiving chronic constriction injury (CCI) of the sciatic nerve. T lymphocyte function was evaluated based on concanavalin-A (ConA)- and phytohemagglutinin (PHA)-induced splenocyte proliferation. NK cell activity was measured by lactic acid dehydrogenase release assay. The effects of tramadol on thermal hyperalgesia were also assessed by measuring paw withdrawal latency (PWL) in the rats. PWL was dose-dependently reversed by tramadol after acute treatment (single subcutaneous injection) with 10, 20, and 30 mg/kg, respectively. There was no significant change among acute treatment groups in NK cell activity, whereas splenocyte proliferation induced by ConA and PHA was significantly suppressed starting from a dose of 20 mg/kg. The reversal of the thermal hyperalgesia persisted throughout a period of chronic tramadol treatment of 40 and 80 mg/kg per day, respectively, with continuous subcutaneous infusion for 7 days at a uniform rate via osmotic minipumps. No modulation of NK cell activity was found in either dose group. However, the activity of splenocyte proliferation was decreased in the 80 mg/kg per day group when compared with the saline and 40 mg/kg per day groups. These data suggest that tramadol treatment has an immunological profile different from pure mu-opioid agonists like morphine, which is known to suppress both NK cell activity and T lymphocyte proliferation at a subanalgesic dose in CCI rats. Considering analgesic and immunosuppressive effects, tramadol treatment may be a better choice than morphine for treatment of chronic neuropathic pain, particularly in patients with compromised immunity.
Article
Sponges composed of sodium alginate and chitosan were prepared via a freeze drying process in order to assess the utility of mixed sponges as potential wound dressings or matrices for tissue engineering. Sponge preparation involved dissolving both polymers (either individually or mixed) in 1% acetic acid and freeze-drying the corresponding solutions. The mechanical properties of the sponges were assessed using texture analysis and the microstructure examined using scanning electron microscopy. The dissolution of a model drug (paracetamol) from the sponges was assessed as a function of polysaccharide composition. It was noted that the sponges had a flexible yet strong texture, as assessed macroscopically. Measurement of the resistance to compression ('hardness') indicated that the chitosan sponges were the 'hardest' while the alginate sponges showed the least resistance to compression, with all sponges showing a high degree of recovery. In contrast, the breaking force (tensile force) of the sponges were greatest for the single component systems, while the elongation prior to breaking was similar for each material. SEM studies indicated that the mixed systems had a less well-defined microstructure than the single component sponges. This was ascribed to the two polysaccharides interacting in aqueous solution via coulombic forces, leading to a more randomly ordered network being formed on freezing. Dissolution studies indicated that systems containing chitosan alone showed the slowest release profile, with the mixed systems showing a relatively rapid dissolution profile. The use of chitosan and alginates together, therefore, appears to allow the formulator to manipulate both the mechanical properties and the drug release properties of the sponges.
Article
The release of a drug from a transdermal delivery system with a rate controlling chitosan membrane was analyzed in vitro and in vivo. Lidocaine hydrochloride, a local anesthetic, was used as the model drug. The in vitro permeability of various chitosan membranes for the drug was investigated using a Franz diffusion cell. Drug release was slower through chitosan membranes with a higher degree of deacetylation (% DD) and with a larger thickness. A transdermal chitosan patch was developed using a chitosan membrane for rate control and a chitosan hydrogel as a drug reservoir. The most prolonged release in vitro was obtained with a 95% DD chitosan rate controlling membrane. The transport mechanism was found to be non-Fickian. The functionality of this transdermal patch was studied on the forearm of human volunteers by assessing the anesthetic effect. Patches with 70% and 95% DD membranes delayed the anesthetic effect, increasing the delay with increasing % DD. It was concluded that a combination of chitosan membrane and chitosan hydrogel is a good transparent system for controlled drug delivery and that the release kinetics in vitro at least for lidocaine have a predictive value for its anesthetic effect in vivo. The demonstration of a direct relationship between in vitro drug membrane permeability and its physiological effect might be considered as quite unique.
Article
Cross-linked chitosan sponges as controlled release drug carrier systems were developed. Tramadol hydrochloride, a centrally acting analgesic, was used as a model drug. The sponges were prepared by freeze-drying 1.25% and 2.5% (w/w) high and low M.wt. chitosan solutions, respectively, using glutaraldehyde as a cross-linking agent. The hardness of the prepared sponges was a function of glutaraldehyde concentration and volume where the optimum concentration that offered accepted sponge consistency was 5%. Below or above 5%, very soft or very hard and brittle sponges were obtained, respectively. The determined drug content in the prepared sponges was uniform and did not deviate markedly from the calculated amount. Scanning electron microscopy (SEM) was used to characterize the internal structures of the sponges. The SEM photos revealed that cross-linked high M.wt. chitosan sponges have larger size surface pores that form connections (channels) with the interior of the sponge than cross-linked low M.wt. ones. Moreover, crystals of the incorporated Tramadol hydrochloride were detected on the lamellae and within pores in both chitosan sponges. Differences in pore size and dissolution medium uptake capacity were crucial factors for the more delayed drug release from cross-linked low M.wt. chitosan sponges over high M.wt. ones at pH 7.4. Kinetic analysis of the release data using linear regression followed the Higuchi diffusion model over 12 hours. Setting storage conditions at room temperature under 80-92% relative humidity resulted in soft, elastic, and compressible sponges.
Article
A chitosan derivative as an acetate salt was successfully prepared by using a spray drying technique. Physicochemical characteristics and micromeritic properties of spray-dried chitosan acetate (SD-CSA) were studied as well as drug-polymer and excipient-polymer interaction. SD-CSA was spherical agglomerates with rough surface and less than 75 microm in diameter. The salt was an amorphous solid with slight to moderate hygroscopicity. The results of Fourier transform infrared (FTIR) and solid-state (13)C NMR spectroscopy demonstrated the functional groups of an acetate salt in its molecular structure. DSC and TGA thermograms of SD-CSA as well as FTIR and NMR spectrum of the salt, heated at 120 degrees C for 12 h, revealed the evidence of the conversion of chitosan acetate molecular structure to N-acetylglucosamine at higher temperature. No interaction of SD-CSA with either drugs (salicylic acid and theophylline) or selected pharmaceutical excipients were observed in the study using DSC method. As a wet granulation binder, SD-CSA gave theophylline granules with good flowability (according to the value of angle of repose, Carr's index, and Hausner ratio) and an excellent compressibility profile comparable to a pharmaceutical binder, PVP K30. In vitro release study of theophylline from the tablets containing 3% w/w SD-CSA as a binder demonstrated sustained drug release in all media. Cumulative drug released in 0.1 N HCl, pH 6.8 phosphate buffer and distilled water was nearly 100% within 6, 16 and 24 h, respectively. It was suggested that the simple incorporation of spray-dried chitosan acetate as a tablet binder could give rise to controlled drug delivery systems exhibiting sustained drug release.
Article
Chitosan has a high potential for transferring DNA molecules into mammalian cells because of its cationic properties. In the present study, we have investigated DNA encapsulation efficiency and loading capacity of chitosan microparticles prepared in different conditions, as well as in vitro DNA release from microparticles, and transfection of different cell lines with chitosan-DNA microparticles, which may be employed in future in vivo studies. Plasmid DNAs were amplified in Escherichia coli DH5alpha and isolated by the alkali SDS-lysis method. Chitosan-DNA microparticles were prepared by the coacervation method by using different concentrations of chitosan and plasmid DNAs. In vitro release experiments were performed in PBS at 37 degrees C and DNA release was monitored spectrophotometrically. Transfection efficiency of chitosan-DNA microparticles into mammalian cells was determined by measuring the beta-galactosidase activity in cell lysates. DNA encapsulation efficiency and loading capacity of microparticles was altered depending on the chitosan and DNA concentrations. Approximately 75-85% of DNA was encapsulated into the chitosan-DNA microparticles. The average size of microparticles was found to be approximately 2 microm. In vitro studies revealed that the release of DNA from chitosan microparticles could be controlled by changing the formulation conditions. Although the transfection efficiency of chitosan-DNA microparticles was typically lower than that of DNA complexed with lipid-based reagents, in vitro transfection results indicated that HEK293 cells take up chitosan-DNA microparticles more efficiently compared to HeLa and mouse fibroblastic 3T3 cell lines. Conclusion: Chitosan microparticles provide a sustained release of plasmid DNA for a long period and they have a potential for DNA transfer into the mammalian cells. However, transfection efficiency of chitosan-DNA microparticles is low and dependent on the cell type.
Article
Recently, considerable interest has been focussed on the use of biodegradable polymers for specialized applications such as controlled release of drug formulations; meanwhile, microsphere drug delivery systems using various kinds of biodegradable polymers have been studied extensively during the past two decades. In the present investigation, it was aimed to prepare microsphere formulations of celecoxib using a natural polymer, chitosan as a carrier for intra-articular administration to extend the retention of the drug in the knee joint. Microsphere formulations were evaluated in vitro for particle size, entrapment efficiency, surface morphology and in vitro drug release. For in vivo studies, (99m)Technetium- labeled glutathione was used as a radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. Evaluation of arthritic lesions post therapy in rats showed a significant difference (P < 0.005) in the group treated with celecoxib solution compared to the group treated with celecoxib loaded chitosan microspheres.
The preparation and characterization of drug loaded alginate and chitosan sponges
  • H L Lai
  • A Khalil
  • D Q Carig
Lai, H. L., Abu Khalil, A., & Carig, D. Q. (2003). The preparation and characterization of drug loaded alginate and chitosan sponges. Int. J. Pharm., 251(1–2), 175–181.
Chitosan microspheres and sponges for diverse medical applications: Preparation and charac-terization
  • E B Denkbas
  • M Obadasy
Denkbas, E. B., & Obadasy, M. (2000). Chitosan microspheres and sponges for diverse medical applications: Preparation and charac-terization. J. App. Pol. Sci., 76, 1637–1643.
Mechanism of sustained action medication
  • T J Higuchi
Higuchi, T. J. (1963). Mechanism of sustained action medication. J. Pharm. Sci., 52, 1145–1149.
Protein stabilized foams and emulsions. Critical reviews in food science and nutrition
  • P J Halling
  • T E Furia
The Merck Index, An Encyclopedia of Chemicals, Drugs and Biologicals, 11th
  • O ' Neil
  • J M Smith
  • Patricia Heckelman
Clarke's Isolation and Identification of Drugs, 2nd
  • A C Moffat
  • J V Jackson
  • M S Moss
  • B Widdop