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Preparation and characterization of metformin proniosomal gel for treatment of diabetes mellitus

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Abstract

The aim of the investigation was to design a proniosomal carrier system of metformin hydrochloride for the treatment of type - 2 diabetes mellitus that is capable of delivering entrapped drug over an extended period of time. Proniosomes of metformin hydrochloride were prepared by coacervation phase separation method. The potential of proniosomes as a transdermal drug delivery system was estimated by encapsulating the drug in various formulations of proniosomal gel composed of different ratios of Span 60/Span 40, cholesterol and lecithin. The prepared systems were characterized for encapsulation efficiency, size, zeta potential analysis, in-vitro drug release and vesicular stability at different storage conditions. Stability studies for proniosomal gel were carried out for one month. Proniosomes were also characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for shape and surface morphology. The results showed that the encapsulation efficiency of proniosomes prepared with span 60 was superior to that prepared with Span 40. A formulation (i.e. PNG2) with 9:2:9 ratio of span 60, cholesterol and lecithin gave maximum encapsulation efficiency (76.8 %), good zeta potential (-51.9) and lowest drug release percent after 24 hrs (75.9%). It is evident from the study that the metformin proniosomal gel is promising prolonged drug delivery system and has reasonably good stability characteristics.

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... Metformin has short half life of 4-6 hours with oral bioavailability of about 50-60%. Therefore frequent dosing is required but it results in high incidence of gastro intestinal side effects 15 . The most severe side effects of Metformin relates to its association with lactic acidosis. ...
... Metformin also cause gastrointestinal side effects, including vomiting, diarrhea, abdominal pain, drowsiness, stomach pain, flatulence and loss of appetite 12 . Thus the development of suitable drug delivery system for Diabetes mellitus, which will maintain a proper blood level for a long period of time without adverse effects connected with frequent oral administration, is very important 15 . Advantage of using proniosomes of Metformin transdermally is its ability to bypass the gastrointestinal system. ...
... Mixture was further warmed. The mixture was allowed to cool at room temperature, until the dispersion was converted to proniosomal gel 15 . Preparation of transdermal patch containing proniosomes 4gm of PVA was dissolved in 100ml water and the solution was poured on to the mould wrapped with aluminium foil and dried at 60 for 6 hours in an oven. ...
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The aim of the present study is to develop transdermal patch loaded with proniosomes that is capable of delivering the entrapped drug over an extended period of time. Metformin HCl, a hydrophilic drug used for the treatment of type 2 diabetes mellitus. Metformin HCl has short half life of 4-6 hrs with oral bioavailability of about 50-60%. Proniosomal TDDS can overcome the permeation barrier of the skin and enhance the permeation of therapeutically active drug molecule. Metformin hydrochloride proniosomes was prepared by coacervation phase separation method using span 40, span 60, cholesterol and soya lecithin. In this study 6 formulations of proniosomes were prepared and their characteristics such as physical appearance, pH, viscosity, particle size, zeta potential, encapsulation efficiency, surface morphology, drug content and in-vitro drug release studies were investigated. FT-IR study confirmed the drug-polymer compatibility. Particle size of proniosome was obtained in nanometers. Zeta potential of formulation was found negative indicating the stability of the proniosome. F2 showed higher encapsulation efficiency (87.08 ±0.35) and % CDR (64.22%). Proniosomal formulation F2 was selected and converted into transdermal patches using PVA as backing membrane, HPMC E50 and PVP k30 as rate controlling membrane. Evaluation studies like thickness, weight uniformity, folding endurance, % moisture content, drug content and in vitro drug release studies were carried out. The formulation FPT2 showed higher drug content of 17.14 ± 0.32 mg and maximum drug release of 60.58% in 8 hrs. From the data obtained in this study, it was concluded that transdermal patch loaded with proniosomes of Metformin HCl are promising for sustained drug delivery
... Phytosomes provided a sustained release of extract and prevented the increase in the blood glucose level [149] Berberine Solvent evaporation method The improved oral bioavailability of the drug [150] Potentially useful for prolonged drug delivery and impart controlled systemic transdermal delivery of metformin hydrochloride [154] Hydroxy propyl methyl cellulose (HPMC), Ethyl cellulose (EC), Polyethylene glycol (PEG) ...
Article
Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the β cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication’s traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin.
... Metformin hydrochloride is frequently made into a low dosage proniosomal gel for transdermal administration, which protects the receiver from the dangers of high doses while improving absorption. Metformin hydrochloride-consisting of proniosomal carrier system was developed for the therapy of type II diabetes mellitus that can administer entrapped medication over a longer duration [68]. ...
... So far, only limited effort has been made to investigate the transdermal delivery of metformin. Loona et al. [10] prepared a proniosomal carrier system of MetHCl as a transdermal drug delivery system. James and others [11] prepared a controlled release matrix type transdermal patch of MetHCl. ...
Article
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Purpose The purpose of the present study was to explore the feasibility of transdermal delivery of metformin, a commonly used oral antidiabetic drug, by ionic liquid (IL) technology. Methods Metformin hydrochloride (MetHCl) was first transformed into three kinds of ILs with different counterions. The physicochemical properties of the obtained ILs were characterized in depth. The simulation of stable configuration and calculation of interaction energies were conducted based on density functional theory (DFT). Skin-PAMPA was used to evaluate the intrinsic transdermal permeation properties. The cytotoxicity assay of these ILs was conducted using HaCaT cells to evaluate the toxicity to skin. These metformin ILs were then formulated into transdermal patch, and the transdermal potential was further evaluated using in vitro dissolution test and skin permeation assay. Finally, the pharmacokinetic profiles of these metformin IL-containing patches were determined. Results Among all the three Met ILs, metformin dihexyl sulfosuccinate (MetDH) with proper overall physiochemical and biological properties demonstrated the highest relative bioavailability. Metformin docusate (MetD) with the highest lipophilicity and intrinsic transdermal permeability exhibited the most significant sustained release profile in vivo. Both MetDH and MetD were the promising candidates for further clinical investigations. Conclusions Overall, the properties of ILs were closely related to the structures of counterion. IL technology provided the opportunities to finely tune the solid-state and biological properties of Metformin and facilitated the successful delivery by transdermal route.
... Tenoxicam Anti-inflammatory properties The investigated proniosomal gel proved superior to the oral market tablets in anti-inflamatory action [20] Ketorolac NSAIDs Proniosomes prepared with span 60 provided a higher ketorolac flux across the skin than did those prepared with Tween 20 [40] Guggul lipid Herbal Proved superior to the NSAIDS exiting in the market [96] Levonorgestrel Contraceptive agent The study demonstrated the utility of proniosomal transdermal patch bearing levonorgestrel for effective contraception [32] Estradiol Hormonal insufficiencies The encapsulation (%) of proniosomes with Span surfactants showed a very high value of 100%. [30] Carvedilol Antihypertensive Proniosomal gel for improved transdermal delivery were investingated using various surfactants [97] Tacrolimus Immunosuppressive agent Proniosome-derived niosomes may b e a promising vehicle for effective ocular drug delivery of tacrolimus [98] Valsartan Antihypertenive The encapsulation efficiency of span 60 was superior to span 40 [99] Metformin Anti-diabetic agent Metformin proniosomal gel is promising prolonged drug delivery system and has reasonably good stability characteristics [100] Celecoxib NSAIDs The pronisomal formulation improved the extent of absorption than conventional capsules [90] Neem seed oil Therapeutic and cosmetic agent ...
... Liraglutide poly (lactic-co-glycolic acid) [PLGA] nanoparticles Encapsulation of liraglutide in PLGA nanoparticle not only prevented the degradation of the drug by the intestinal enzymes but also increased the intestinal epithelial permeability and thereby enhanced the bioavailability and efficacy of liraglutide administered orally. [239] (continued on next page) Sustained release of metformin was observed till 10 hrs with high drug entrapment efficiency [254] propylene glycol, Polymethacrylic acid and soya Lecithin ...
Article
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Diabetes mellitus (DM) is a metabolic disorder that occurs in the body because of decreased insulin activity and/or insulin secretion. Pathological changes such as nephropathy, retinopathy, and cardiovascular complications inevitably occur in the body with the progression of the disease. DM is mainly categorized into 2 sub-types, type I DM and type II DM. While type I DM is generally treated through insulin replacement therapy, type II DM is treated with oral hypoglycaemics. The major drug therapy for type II DM comprises of insulin secretagogues, biguanides, insulin sensitizers, alpha glucosidase inhibitors, incretin mimetics, amylin antagonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors. Dual drug therapies are often recommended in patients who are unable to achieve therapeutic goals with first line oral hypoglycaemic agents as monotherapy. Inspite of the appreciable therapeutic benefits, the conventional dosage forms depicts differential bioavailability and short half-life, mandating frequent dosage and causing greater side effects leading to therapy ineffectiveness and patient non-compliance. Given the pathological complexity of the said disease, nanotechnology-based approaches are more enticing as it comes with added advantage of site-specific drug delivery with higher bioavailability and reduced dosage regimen. In the present review article, we have made an attempt to explore the pathophysiology of type II DM, the conventional treatment approaches (mono and combination therapy) as well as the nano based drug delivery approaches for the treatment of type II DM.
... Most studies on metformin-HCl have been correlated with oral and injectable use. There are a few reports on the topical application of metformin-HCl to skin tissue, most of which have aimed to reduce blood glucose level in diabetic patients [32,33], increase drug permeability to the skin [34,35], and augment wound healing in diabetic patients [36,37]. Moreover, topical metformin-HCl application to reduce/prevent skin scar formation has not been performed. ...
Article
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Abnormal wound healing caused by the over-expression of collagen and fibronectin leads to fibrosis, the major complication of all treatment modalities. A three-layer nanofiber scaffold was designed, optimized, and fabricated. This scaffold comprised two supportive polycaprolactone (PCL)-chitosan layers on the sides and a polyvinyl alcohol (PVA)-metformin hydrochloride (metformin-HCl) in the middle. The physico-chemical properties of scaffold, such as mechanical characteristics, degradation, swelling, and in-vitro drug release, were evaluated. The biological tests, including cell viability in response to metformin-HCl and Tween 80, scaffold biocompatibility, cell attachment, and antibacterial activity, were further conducted. The wound healing effect of scaffold loaded with metformin-HCl (MSc+Met) was assessed in donut-shaped silicone splints in rats. Histopathological and immunohistochemical evaluation as well as mRNA expression levels of fibrosis markers were also studied. SEM images indicated a uniform, bead-less morphology and high porosity. Surface modification of scaffold by Tween 80 improved the surface hydrophilicity and enhanced the adhesion and proliferation of fibroblasts. The scar area on day 15 in MSc+Met was significantly lower than that of other groups. Histopathological and immunohistochemical evaluation revealed that group MSc+Met was the best, having significantly lower inflammation, higher angiogenesis, the smallest scar width and depth, maximum epitheliogenesis score, and the most optimal modulation of collagen density. Local administration of metformin-HCl substantially down-regulated the expression of fibrosis-involved genes: transforming growth factor (TGF-β1), collagen type 1 (Col-I), fibronectin, collagen type 3 (Col-III), and alpha-smooth muscle actin (α-SMA). Inhibiting these genes alleviates scar formation but delays wound healing; thus, an engineered scaffold was used to prevent delay in wound healing. These results provided evidence for the first time to introduce an anti-fibrogenic slow-releasing scaffold, which acts in a dual role, both alleviating fibrosis and accelerating wound healing.
... Accurate weight of curcumin proniosomes was hydrated 100 times with distilled water. The resulted colloid was sonicated (30 min) (USR3, Julabo Labortechnik, Seelbach, West Germany) then analyzed by adding the produced niosomes (1 mL) into a Malvern's disposable vial [33]. ...
Article
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Curcumin is a dietary compound with accrued evidence of antiviral activity. Poor solubility and permeation renders curcumin a good applicant for incorporation into proniosomes. The intent of this study was to formulate curcumin proniosomal gel for topical application and the evaluation of its in-vitro, ex-vivo activities against Herpes Simplex virus type 1 (HSV-1), as well as molecular docking studies on HSV-1 thymidine kinase proteins. Coacervation phase separation tactic, using 2 3 full factorial design, was used in the preparation of different proniosomes. Cytotoxicity of the selected formulae (F4 and F8) was evaluated on the Vero cell line. Optimal formulae (F4 and F8) showed entrapment efficiency of 97.15 ± 2.47% and 95.85 ± 2.9%, vesicle size of 173.7 ± 2.26 nm and 206.15 ± 4.17 nm and percentages curcumin released after 3 h of 51.9 ± 1.4% and 50.5 ± 1.1%, respectively. Ex-vivo permeation studies demonstrated that the optimal formulae markedly improved the dermal curcumin delivery. Curcumin proniosomal gel formulae exhibited 85.4% reduction of HSV-1 replication. The ability of curcumin to interact with the key amino acids in the enzyme binding sites of 1KI7, 1KI4, and 1E2P, as indicated by its docking pattern, rationalized its observed activity. Therefore, curcumin proniosomes could be considered as a successful topical delivery system for the treatment of HSV-1.
... Niosomal formulations protect the drug and extend its duration of action due to the slow controlled release of the encapsulated drug. Also the transdermal route offers a unique advantage of maintaining the drug levels for an longer period of time in blood than oral route, alleviates its gastrointestinal symptoms and bypass the first pass metabolism (Loona et al. 2012, Madhavi et al. 2013, Sharma et al. 2013. During the preparation of such formulations, Tween 80 was added in different proportions to different nonionic surfactants' combinations to detect the ability of HLB shifting of the formulations to increase the entrapment of hydrophilic drugs like metformin HCl. ...
Article
Niosomes as drug delivery systems have the ability to decrease drugs' side effects and increase their therapeutic effectiveness. Metformin HCl is an oral anti-hyperglycemic agent belonging to biguanides. It is the most commonly chosen drug as a start-up therapy for patients newly diagnosed with type 2 diabetes. This study aims to encapsulate metformin HCl inside niosomes to be used as a transdermal formulation helping to prolong its anti-diabetic effect and investigate its ability to enhance wound healing in diabetic patients. Thin film hydration method was used to prepare metformin HCl niosomes using different proportions of Span 60, Span 40, Tween 80 and cholesterol. All formulations were characterized using transmission electron microscope, zeta potential and vesicle size. In-vitro release studies, stability studies and in-vivo evaluation were conducted on selected niosomal formulations. The results of entrapment efficiency ranged from 13% to 32%. Vesicle sizes were determined in nano-range. The in-vitro release profile of metformin HCl from niosomes occurred in two consecutive phases. Biological evaluation on diabetic rats revealed that metformin HCl niosomal gel given every two days showed a better sustained anti-diabetic effect than oral doses given daily. It also showed an improvement in wound healing for diabetic rats given metformin formulations compared to non-treated ones.
... Nanoformulations in Transdermal patches (TDP) Metformin Soya Lecithin, Span 60 (31.1 ± 1.11 nm) and Span 40 (16.8 ± 0.92 nm) proniosomal gel - Sustained release till 10 h, high entrapment with controlled delivery [204] SLNs of propylene glycol, Polymethacrylic acid and soya lecithin (12 ± 8-242 ± 5 nm) improved bioavailability [58]. This has been illustrated in a study by Kumar et al. wherein, metformin loaded sodium alginate NPs exhibited a 100% drug release within 30 min as compared to free drug (1h) in vitro, and when administered orally in diabetic ani- mals, proved three times more efficacious than free metformin given intraperitoneally (i.p.) [40]. ...
Article
Emergence of nanoparticulate drug delivery systems in diabetes has facilitated improved delivery of small molecule drugs which could dramatically improve the quality of life for diabetics. Conventional dosage forms of the anti-diabetic drugs exhibit variable/less bioavailability and short half-life, demanding frequent dosing and causing increased side-effects resulting in ineffectiveness of therapy and non-compliance with the patients. Considering the chronic nature of diabetes, nanotechnology-based approaches are more promising in terms of providing site-specific delivery of drugs with higher bioavailability and reduced dosage regimen. Nanomedicines act at the cellular and molecular levels to enhance the uptake of the drug into the cells or block the efflux mechanisms thus retaining the drug inside the cell for a longer duration of time. Many studies have hinted at the possibility of administering peptide drugs like glucagon like peptides orally by encapsulation into nanoparticles. Nanoparticles also allow further modifications including their encapsulation into microparticles, polyethylene glycol (PEG)- PEGylation- or functionalization with ligands for active targeting. Nevertheless, such remarkable benefits are fraught with their long-term safety concerns, regulatory hurdles, limitations of scale-up and ineffective patent protection which have hindered their commercialization. This review summarizes the latest advances in the area of nanoformulations as applied to the delivery of anti-diabetics. Statement of significance: The present work describes the latest advancements in the area of nanoformulations for anti-diabetic therapy along with highlighting the advantages that these nanoformulations offer at molecular level for diabetes. Although several potent orally active anti-hyperglycemic agents are available, the current challenges in efficient management of diabetes include optimization of the present therapies to ensure an optimum and stable level of glucose, and also to reduce the occurrence of long term complications associated with diabetes. Nanoformulations because of their high surface area to volume ratio provide improved efficacy, targeting their delivery to the desired site of action tends to minimize adverse effects and administration of peptide drugs by oral route is also possible by encapsulating them in nanoparticles. As we reflect on the success and failures of latest research on nanoformulations for the treatment of diabetes, it is important not to dwell on lack of FDA approvals but rather define future directions that guarantee more effective anti-diabetic treatment. In proposed review we have explored the latest advancement in anti-diabetic nanotechnology based formulations.
... 4 Regarding the applications of transdermal proniosomes in diabetes: Gupta et al. concluded that metformin proniosomal gel is promising prolonged drug delivery system. 5 The Aim of the present study was to prepare and evaluate transdermal GM loaded proniosomal gel. Drug entrapment efficiency, release profiles, ex-vivo skin permeation and in-vivo hypoglycemic activity were evaluated. ...
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Objective: The aim of this study is to formulate and evaluate proniosomal gel formulations as transdermal delivery systems of glimepiride (GM) to improve its therapeutic efficacy. Methods: Proniosomal formulations have been prepared using different types of non-ionic surfactants with cholesterol in different molar ratios. Proniosomal gel; PN16 (Span 60, Tween 60, Cholesterol; 35:35:30 molar ratio) that exhibits maximum EE % (94.01 ± 0.88) and most prolonged release was chosen for ex-vivo skin permeation and in-vivo hypoglycemic activity studies. Results: Proniosomal gel produced better permeation through rabbit skin than HPMC niosomal gel and HPMC gel. The pharmacokinetic parameters; time of maximum response (Tmax), % reduction in blood glucose concentration and area above the blood glucose levels-time curve (AAC) of proniosomal gel were studied. Proniosomal gel showed a controlled release behavior and a significantly higher hypoglycemic activity (65.34 ± 6.54%). Conclusion: It is evident from this study that proniosomal gel can act as an alternative approach for enhancing transdermal delivery of GM.
... The use of niosomes for loading a single anti-diabetic drug for sustained release has been extensively investigated. Furthermore, metformin HCl loaded niosomal and proniosomal formulations with sustained release of 8-12 h have been developed [14][15][16][17][18]. As far as hydrophobic antidiabetic drugs are concerned, sustained release of glipizide and glicalizide (another sulphonyl urea drug) has been achieved in niosomal formulations [19,20]. ...
... Tenoxicam Anti-inflammatory properties The investigated proniosomal gel proved superior to the oral market tablets in anti-inflamatory action [20] Ketorolac NSAIDs Proniosomes prepared with span 60 provided a higher ketorolac flux across the skin than did those prepared with Tween 20 [40] Guggul lipid Herbal Proved superior to the NSAIDS exiting in the market [96] Levonorgestrel Contraceptive agent The study demonstrated the utility of proniosomal transdermal patch bearing levonorgestrel for effective contraception [32] Estradiol Hormonal insufficiencies The encapsulation (%) of proniosomes with Span surfactants showed a very high value of 100%. [30] Carvedilol Antihypertensive Proniosomal gel for improved transdermal delivery were investingated using various surfactants [97] Tacrolimus Immunosuppressive agent Proniosome-derived niosomes may b e a promising vehicle for effective ocular drug delivery of tacrolimus [98] Valsartan Antihypertenive The encapsulation efficiency of span 60 was superior to span 40 [99] Metformin Anti-diabetic agent Metformin proniosomal gel is promising prolonged drug delivery system and has reasonably good stability characteristics [100] Celecoxib NSAIDs The pronisomal formulation improved the extent of absorption than conventional capsules [90] Neem seed oil Therapeutic and cosmetic agent ...
Article
Full-text available
Vesicular systems are a novel means of drug delivery that can enhance the bioavailability of encapsulated drug and provide therapeutic activity in a controlled manner for a prolonged period of time. Liposomes were the first such system, but they suffer from a number of drawbacks including high cost and lack of stability at various pHs. To avoid the drawback of liposomes, niosomes were invented, which can be easily and reliably made in the laboratory. Niosomes are the ideal means of drug delivery that can enhance the bioavailability of encapsulated drug by various mechanisms and provide a therapeutic activity for a prolonged period of time. However, they suffer from aggregation, fusion, leaking, sedimentation of vesicles, and difficulty in sterilization; so to overcome these problems, a newer approach was employed which is known as pro-vesicular carriers. Here, in this review, we elaborate one of the pro-vesicular carriers, widely known as proniosome. This review covers all the aspects of proniosomes including mechanism, formulation variables and their effects, methods of preparation, parameters for characterizations, and application.
... Tenoxicam Anti-inflammatory properties The investigated proniosomal gel proved superior to the oral market tablets in anti-inflamatory action [20] Ketorolac NSAIDs Proniosomes prepared with span 60 provided a higher ketorolac flux across the skin than did those prepared with Tween 20 [40] Guggul lipid Herbal Proved superior to the NSAIDS exiting in the market [96] Levonorgestrel Contraceptive agent The study demonstrated the utility of proniosomal transdermal patch bearing levonorgestrel for effective contraception [32] Estradiol Hormonal insufficiencies The encapsulation (%) of proniosomes with Span surfactants showed a very high value of 100%. [30] Carvedilol Antihypertensive Proniosomal gel for improved transdermal delivery were investingated using various surfactants [97] Tacrolimus Immunosuppressive agent Proniosome-derived niosomes may b e a promising vehicle for effective ocular drug delivery of tacrolimus [98] Valsartan Antihypertenive The encapsulation efficiency of span 60 was superior to span 40 [99] Metformin Anti-diabetic agent Metformin proniosomal gel is promising prolonged drug delivery system and has reasonably good stability characteristics [100] Celecoxib NSAIDs The pronisomal formulation improved the extent of absorption than conventional capsules [90] Neem seed oil Therapeutic and cosmetic agent ...
... 4 Regarding the applications of transdermal proniosomes in diabetes: Gupta et al. concluded that metformin proniosomal gel is promising prolonged drug delivery system. 5 The Aim of the present study was to prepare and evaluate transdermal GM loaded proniosomal gel. Drug entrapment efficiency, release profiles, ex-vivo skin permeation and in-vivo hypoglycemic activity were evaluated. ...
Article
Full-text available
Objective: The aim of this study is to formulate and evaluate proniosomal gel formulations as transdermal delivery systems of glimepiride (GM) to improve its therapeutic efficacy. Methods: Proniosomal formulations have been prepared using different types of non-ionic surfactants with cholesterol in different molar ratios. Proniosomal gel; PN16 (Span 60, Tween 60, Cholesterol; 35:35:30 molar ratio) that exhibits maximum EE % (94.01 ± 0.88) and most prolonged release was chosen for ex-vivo skin permeation and in-vivo hypoglycemic activity studies. Results: Proniosomal gel produced better permeation through rabbit skin than HPMC niosomal gel and HPMC gel. The pharmacokinetic parameters; time of maximum response (Tmax), % reduction in blood glucose concentration and area above the blood glucose levels-time curve (AAC) of proniosomal gel were studied. Proniosomal gel showed a control led release behavior and a significantly higher hypoglycemic activity (65.34 ± 6.54%). Conclusion: It is evident from this study that proniosomal gel can act as an alternative approach for enhancing transdermal delivery of GM.
Article
Currently, various kinds of research are going in the evolution of the Novel Drug Delivery System. NDDS mainly emphasizes the development of a system with improved sustained, controlled, and targeted drug delivery with minimum toxicity. Proniosomes are dry free-flowing formulation that minimizes the drawbacks associated with liposomes and niosomes. Proniosomes are carrier particles that are water-soluble and covered with a surfactant which upon hydration in a hot aqueous medium with agitation gives niosomal dispersion. Proniosomes derived niosomes are superior substitutes as compared to other vesicular delivery due to preferable physicochemical properties and improved chemical stability. The proniosomes deliver additional convenience of transportation, storage, distribution, and dosing which makes dry niosomes a versatile commercial product. This illustrated review emphasizes the components, method of preparation, factors affecting the formation of proniosomes, characterization, and various routes of administration of proniosomes. This review will help you to explore the efficacy and functionality of proniosomes in different fields for their upcoming supremacy in the field of drug delivery.
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Proniosomes are the stable carriers used for Transdermal application as compared to other vesicular delivery systems like niosomes and liposomes. Oral administration of a drug is associated severe GIT irritation and first pass metabolism. Vesicular drug delivery system includes basic concept of niosomes and proniosomes which describe their mechanism of action, structural formation, interactive study with skin, composition, method of preparation. Gels contains high aqueous component as compared to ointment and creams, due to which it can dissolve high concentration of drugs, and thus helps the drug to migrate easily through a vehicle.th this respect gels are considered to be superior in terms of use and patient compliance. This review will focus on the up to date research development, which are applicable to various diseases by using of proniosomes. Proniosomes are prepared mainly by different concentrations of nonionic surfactant, cholesterol, lecithin by entrapping hydrophobic as well as hydrophilic drugs. In earlier studies it was found that the non ionic surfactants and phospholipids which provided higher penetration since it had been found that some phospholipids have the ability to fluidize the lipid bilayer of stratum corneum and diffused through them. In future, Proniosomes can gain more importance in the area of melanoma, brain targeting, protein and peptide drug delivery, gene delivery, hematological drug delivery and also in cosmetics, neutrceuticals.
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Diabetes mellitus is found to be among the most suffered and lethal diseases for mankind. Diabetes mellitus type-1 is caused by the demolition of pancreatic islets responsible for the secretion of insulin. Insulin is the peptide hormone (anabolic] that regulates the metabolism of carbohydrates, fats, and proteins. Upon the breakdown of the natural process of metabolism, the condition leads to hyperglycemia (increased blood glucose levels]. Hyperglycemia demands outsourcing of insulin. The subcutaneous route was found to be the most stable route of insulin administration but faces patient compliance problems. Oral Insulin delivery systems are the patient-centered and innovative novel drug delivery system, eliminating the pain caused by the subcutaneous route of administration. Insulin comes in contact across various barriers in the gastrointestinal tract, which has been discussed in detail in this review. The review describes about the different bioengineered formulations, including microcarriers, nanocarriers, Self-Microemulsifying drug delivery systems (SMEDDs), Self-Nanoemulsifying drug delivery systems (SNEDDs), polymeric micelles, cochleates, etc. Surface modification of the carriers is also possible by developing ligand anchored bioconjugates. A study on evaluation has shown that the carrier systems facilitate drug encapsulation without tampering the properties of insulin. Carrier-mediated transport by the use of natural, semi-synthetic, and synthetic polymers have shown efficient results in drug delivery by protecting insulin from harmful environment. This makes the formulation readily acceptable for a variety of populations. The present review focuses on the properties, barriers present in the GI tract, overcome the barriers, strategies to formulate oral insulin formulation by enhancing the stability and bioavailability of insulin.
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The aim of the present study was to prepare, optimize and characterize ketoprofen proniosomes. The niosomes were prepared using a slurry method followed by in vitro evaluation after embedding the proniosomes-derived niosomes into a carbopol matrix. A central, composite Box-Wilson design was used for the optimization with the total lipid concentration (X 1), surfactant loading (X 2) and amount of drug (X 3) as the independent variables. Prepared proniosomes were characterized for percentage drug entrapment (PDE) and mean volume diameter (MVD). Multiple regression analysis and contour plots were used to relate the dependent and independent variables. Checkpoint batches were also prepared to prove the validity of the evolved mathematical model and contour plots. The optimization model predicted the levels of X 1 , X 2 and X 3 (-1, -0.3 and 0.92, respectively), for a maximized response of PDE with constraints of ≤ 5 μm on MVD. Optimized batch was used to prepare a niosomal gel, which showed significantly higher cumulative amount of drug permeated and steady state transdermal flux compared to plain gel. This work has demonstrated the use of the central composite Box-Wilson design, regression analysis, and contour plots in optimizing ketoprofen proniosomes. Developed niosomal gel formulation has also demonstrated permeation enhancement of ketoprofen compared to plain gel.
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Niosomes are nonionic surfactant vesicles that have potential applications in the delivery of hydrophobic or amphiphilic drugs. Our lab developed proniosomes, a dry formulation using a sorbitol carrier coated with nonionic surfactant, which can be used to produce niosomes within minutes by the addition of hot water followed by agitation. The sorbitol carrier in the original proniosomes was soluble in the solvent used to deposit surfactant, so preparation was tedious and the dissolved sorbitol interfered with the encapsulation of one model drug. A novel method is reported here for rapid preparation of proniosomes with a wide range of surfactant loading. A slurry method has been developed to produce proniosomes using maltodextrin as the carrier. The time required to produce proniosomes by this simple method is independent of the ratio of surfactant solution to carrier material and appears to be scalable. The flexibility of the proniosome preparation method would allow for the optimization of drug encapsulation in the final formulation based on the type and amount of maltodextrin. This formulation of proniosomes is a practical and simple method of producing niosomes at the point of use for drug delivery.
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The aim of this study was to investigate the combined influence of 3 independent variables in the preparation of piroxicam proniosomes by the slurry method. A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation and construct contour plots to predict responses. The independent variables selected were molar ratio of Span 60:cholesterol (X(1)), surfactant loading (X(2)), and amount of drug (X(3)). Fifteen batches were prepared by the slurry method and evaluated for percentage drug entrapment (PDE) and vesicle size. The transformed values of the independent variables and the PDE (dependent variable) were subjected to multiple regression to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation to derive a reduced-model polynomial equation to predict the PDE of proniosome-derived niosomes. Contour plots were constructed to show the effects of X(1), X(2) and X(3) on the PDE. A model was validated for accurate prediction of the PDE by performing checkpoint analysis. The computer optimization process and contour plots predicted the levels of independent variables X(1), X(2), and X(3) (0, -0.158 and -0.158 respectively), for maximized response of PDE with constraints on vesicle size. The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of piroxicam proniosomes.
Article
In the present study transdermal Lisinopril proniosomal gels was formulated by using Lecithin, Cholesterol as encapsulating agents, Surfactant, Span and permeation enhancers. The study methodology encompasses compatibility studies using FTIR spectra, evaluation of proniosomal gels for pH determination, Viscosity, Vesicle size analysis, rate of spontaneity, encapsulation efficiency, in vitro skin permeation studies and stability studies. The preliminary compatibility studies conducted revealed that there no interaction between Lisinopril and excipients which was as evident from FTIR spectral studies. The physical characterization of proniosomal gels was found to be within the acceptable limits. It was observed that the gel formulations showed good spreadability and viscosity. Determination of vesicle size was found to be 20.10-26.23μm. The proniosomes showed spherical and homogenous structure in optical microscopy. All formulations showed zero order drug release by diffusion mechanism. The stability studies showed that proniosomal gels were stable at 4 to 80C and 25±20C. The above results indicated that the proniosomal gels of could be formulated for controlled release of Lisinopril. The proniosomal gels are suitable for Lisinopril once a day controlled release formulation.
Article
The aim of this investigation was to prepare, characterize and optimize the irinotecan loaded proniosomes for overall improvement in the efficacy, reduced toxicity and enhancement of therapeutic index of irinotecan. Proniosomes of Irinotecan hydrochloride trihydrate were prepared by slurry method using different surfactants, cholesterol and dicetyl phosphate. The formulations were then characterized with respect to shape and surface morphology, entrapment efficiency, invitro drug release profile, invivo drug targeting studies and stability under specific conditions. The formulated proniosomes were smoother indicating a thin and uniform coating over maltodextrin powder. The highest entrapment efficiency was found in formulation F4 with 74.23±3.1%. Highest cumulative percent drug release was observed with formulation F1 with 98.19% in 24 h. The in vivo result of formulated proniosomes of Irinotecan hydrochloride trihydrate reveals that the drug is preferentially targeting to liver followed by lungs and spleen. The results of investigation demonstrated that proniosomes offers an alternative colloidal carrier approach in achieving drug targeting. The results obtained for the present study clearly revealed that proniosomes containing irinotecan are retained at targeted sites and are capable of releasing there drug for the extended period of time.
Article
Purpose: To develop a proniosomal carrier system of curcumin for transdermal delivery.Methods: Proniosomes of curcumin were prepared by encapsulation of the drug in a mixture of Span 80, cholesterol and diethyl ether by ether injection method, and then investigated as a transdermal drug delivery system (TDDS). The formulated systems were characterized for size, drug entrapment, angle of repose, hydration rate and vesicular stability under various storage conditions. In vitro release studies were performed using albino rat skin.Results: The method used for preparing proniosome resulted in an encapsulation yield of 82.3 – 86.8%. Scanning electron microscopy analysis showed that the surface of the particles was smooth. Stability data following storage under different conditions showed that the drug content of the proniosomes varied from 99.5% under refrigerated condition to 99.2 and 93% at room and elevated temperatures, respectively. One of the formulations (PG1) showed prolonged in vitro drug release of 61.8% over aperiod of 24 h.Conclusion: It is evident from this study that proniosomes are very stable and promising prolonged delivery system for curcumin.
Article
Piroxicam is a widely used potent non-steroidal anti-inflammatory drug, with due potential for dermal delivery. Permeation of piroxicam from proniosome based reservoir type transdermal gel formulation across excised rat abdominal skin was investigated using Keshery Chein diffusion cell. There was considerable improvement in flux over the control gel formulation. The lipid vesicles were evaluated for entrapment efficiency and vesicle size of niosomes formed. It was observed that Span 60 based formulations produced vesicles of smallest size and higher entrapment efficiency while those of Span 80 produced vesicles of least entrapment efficiency. Incorporation of lecithin further enhanced entrapment efficiency. Proniosomes were prepared by conventional technique and employing maltodextrin and sorbitol as base. The morphology of the proniosomes was studied by scanning electron microscopy. Maximum flux achieved was 35.61 g/cm 2 /h, an enhancement of 7.39 times was achieved for transdermal system based on proniosomal gel as compared to control gel. Anti-inflammatory studies revealed that proniosome based transdermal drug delivery system of piroxicam were promising carriers for delivery of piroxicam. There was significant reduction in carrageenan induced rat paw inflammation compared to control.
Article
The purpose of the current study was to investigate the feasibility of proniosomes as transdermal drug delivery system for losartan potassium. Different preparations of proniosomes were fabricated using different nonionic surfactants, such as Span 20, Span 40, Span 60, Span 80, Tween 20, Tween 40, and Tween 80. Different formulae were prepared and coded as PNG-1 (proniosomal gel-1) to PNG-7. The best in vitro skin permeation profile was obtained with proniosomal formulation PNG-2 in 24 h. The permeability parameters such as flux, permeability coefficient, and enhancement ratio were significant for PNG-2 compared with other formulations (P < 0.05). This optimized PNG-2 was fabricated in the form of transdermal patch using HPMC gel as a suitable base. Proniosomal transdermal therapeutic system (PNP-H) was found to be the optimized one as it gave better release of drug and better permeation in a steady-state manner over a desired period of time, that is, 24 h through rat skin. In vivo pharmacokinetic study of PNP-H showed a significant increase in bioavailability (1.93 times) compared with oral formulation of losartan potassium. The formulation appeared to be stable when stored at room temperature (30 +/- 2 degrees C) and at refrigeration temperature (4 +/- 2 degrees C) for 45 days.
Article
The treatment of infections caused by obligate or facultative intracellular microorganisms is difficult because most of the available antibiotics have either poor intracellular diffusion and retention or reduced activity at the acidic pH of the lysosomes. The need for antibiotics with greater intracellular efficacy led to the development of endocytosable drug carriers, such as liposomes and nanoparticles, which mimic the entry path of the bacteria by penetrating the cells into phagosomes or lysosomes. This Review assesses the potential of liposomes and nanoparticles in the targeted antibiotic therapy of intracellular bacterial infections and diseases and the pharmaceutical advantages and limitations of these submicron delivery systems.