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Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery

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Abstract

Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.

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... Hydrogels are elastic three-dimensional networks made of water-soluble polymers/small molecules [131,135,136]. The network can consist of natural polymers, that include anionic (e.g. ...
... The leading interactions involved in the network cross-linking or entanglement promote their water insolubility accompanied by the retention of a huge portion of solvent, that ultimately results in gel formation [136,139]. Hereby, the gelation process is characterized by a network expansion due to the capillary, osmotic and solvation forces that are counterbalanced by forces that resist expansion and keep network integrity [132]. The equilibrium between these opposing forces and its magnitude will determine the hydrogel intrinsic properties, such as the internal transport, diffusion characteristics and mechanical strength, which are also governed by the network morphology and chemical nature of the network chains. ...
... The controllable porous structure of hydrogels can be adapted to favor encapsulation of drugs in the matrix, besides modulating its release through changes that affect its diffusion coefficient, which guarantees a high drug concentration in the target site, for a long period of time [133]. Considering the abovementioned hydrogel properties, the applicability in different forms such as rectal [157], nasal [136], topic and intravenous injection can be optimized by adapting the mechanical and shape properties that best fit the required parameters to maximize the overall efficacy and patient compliance (Fig. 5). ...
Article
Magnetic gels have been gaining great attention in nanomedicine, as they combine features of hydrogels and magnetic nanoparticles into a single system. The incorporation of liposomes in magnetic gels further leads to a more robust multifunctional system enabling more functions and spatiotemporal control required for biomedical applications, which includes on-demand drug release. In this review, magnetic gels components are initially introduced, as well as an overview of advancements on the development, tuneability, manipulation and application of these materials. After a discussion of the advantages of combining hydrogels with liposomes, the properties, fabrication strategies and applications of magnetic liposome-hydrogel composites (magnetic lipogels or magnetolipogels) are reviewed. Overall, the progress of magnetic gels towards smart multifunctional materials are emphasized, considering the contributions for future developments.
... Hybrid hydrogel was reported with more than 80 wt % of water content [9]. The involved nanoparticles in the hydrogel still have a nanoscale effect and interface effect [10] that benefits the generation of large-scale physical crosslinking. Moreover, the hybrid hydrogel at the microscale was reported to have a unique three-dimensional network structure that can lock many types of functional elements inside, which shows broad potential applications in areas of biomedical engineering, such as drug carriers, anti-bacterial wound dressing, human cartilage, skin substitute material, medical gel electrodes, etc. [10][11][12][13]. ...
... The involved nanoparticles in the hydrogel still have a nanoscale effect and interface effect [10] that benefits the generation of large-scale physical crosslinking. Moreover, the hybrid hydrogel at the microscale was reported to have a unique three-dimensional network structure that can lock many types of functional elements inside, which shows broad potential applications in areas of biomedical engineering, such as drug carriers, anti-bacterial wound dressing, human cartilage, skin substitute material, medical gel electrodes, etc. [10][11][12][13]. ...
... Hydrogels are similar to natural tissue microenvironments because of their porous and hydrated molecular networks [67]. Hydrogels are widely used as matrix systems to control the release of macromolecules and can be combined with nanoparticles to design new systems, significantly improving the efficiency of drug absorption [68]. Although they have many advantages as a drug delivery system through the nasal administration route, their toxicity is a concern. ...
... A vaccine based on ISCOMs showed a stronger mucosal and cellular immunity after its intranasal immunization [147]. The hydrogel nanoscale system has the characteristics of mucosal adhesion, enabling it to extend residence time, thereby increasing the contact time with the nasal mucosa and enhancing drug absorption [68]. Bedford et al. found that intranasal immunization with a chitosan hydrogel vaccine prolonged the retention time of antigens in the nasal mucosa [148]. ...
Article
Full-text available
Nasal drug delivery is advantageous when compared with other routes of drug delivery as it avoids the hepatic first-pass effect, blood–brain barrier penetration, and compliance issues with parenteral administration. However, nasal administration also has some limitations, such as its low bioavailability due to metabolism on the mucosal surface, and irreversible damage to the nasal mucosa due to the ingredients added into the formula. Moreover, the method of nasal administration is not applicable to all drugs. The current review presents the nasal anatomy and mucosal environment for the nasal delivery of vaccines and drugs, as well as presents various methods for enhancing nasal absorption, and different drug carriers and delivery devices to improve nasal drug delivery. It also presents future prospects on the nasal drug delivery of vaccines and drugs.
... splenic cytokine profiles indicated that S-NPs adjuvanted with the STING agonist potently activate the cell-mediated immune response. (24,48, and 72 h of treatment). "a" indicates significant differences between S-containing vaccines and placebo group. ...
... After 72 h post-treatment, splenocytes were harvested and subjected to measuring the percentages of CD4 + (A) and CD8 + (B) T cells by flow cytometry. Results are mean ± SD. (C) Heat map representing splenic cytokine profiles (IL-2, IFN-γ, and IL-4) from culture supernatant at three consecutive days (24,48, and 72 h of treatment). "a" indicates significant differences between S-containing vaccines and placebo group. ...
Article
Full-text available
The respiratory organ serves as a primary target site for SARS-CoV-2. Thus, the vaccine-stimulating immune response of the respiratory tract is significant in controlling SARS-CoV-2 transmission and disease development. In this study, mucoadhesive nanoparticles were used to deliver SARS-CoV-2 spike proteins (S-NPs) into the nasal tracts of mice. The responses in the respiratory organ and the systemic responses were monitored. The administration of S-NPs along with cGAMP conferred a robust stimulation of antibody responses in the respiratory tract, as demonstrated by an increase of IgA and IgG antibodies toward the spike proteins in bronchoalveolar lavages (BALs) and the lungs. Interestingly, the elicited antibodies were able to neutralize both the wild-type and Delta variant strains of SARS-CoV-2. Significantly, the intranasal immunization also stimulated systemic responses. This is evidenced by the increased production of circulating IgG and IgA, which were able to neutralize and bind specifically to the SARS-CoV-2 virion and spike protein. Additionally, this intranasal administration potently activated a splenic T cell response and the production of Th-1 cytokines, suggesting that this vaccine may well activate a cellular response in the respiratory tract. The results demonstrate that STING agonist strongly acts as an adjuvant to the immunogenicity of S-NPs. This platform may be an ideal vaccine against SARS-CoV-2.
... Hydrogel-loaded nanoformulated drugs have drawn significant attention as promising nanoparticulate drug delivery systems that combine both hydrogel system properties (e.g., hydrophilicity and high water absorption affinity) and nanoparticulate properties (e.g., ultrasmall size) [20][21][22][23][24][25][26][27], can achieve high drug loading without chemical reactions, and are able to release integrated agents at the target site in a controlled behavior. A wide range of natural, naturally derived and synthetic hydrogels can be used for hydrogel-loaded nanoformulated drug preparation [26][27][28]. ...
... Thus, the application of hydrogel-specific properties is now considered to be a useful platform for the preparation of stabilized and smart nanoscopic vehicles for drug delivery purposes. In addition, the incorporation of transferosomes into the hydrogel network can offer remote-controlled applications and also improve characteristics such as mechanical strength [25,42,48,49]. The observed higher extent of absorption from optimized FLB TRF hydrogel compared to the raw FLB gel could be attributed to the drug's improved solubility and permeability by loading on a hydrophobic carrier. ...
Article
Full-text available
Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubility. Aiming at circumventing these drawbacks, this work involves the formulation of optimized FLB transfersome (TRF) loaded intranasal hydrogel. Box–Behnken design was utilized for the improvement of FLB TRFs with decreased size. The FLB-to-phospholipid molar ratio, the edge activator hydrophilic lipophilic balance, and the pH of the hydration medium all exhibited significant effects on the TRF size. The optimized/developed TRFs were unilamellar in shape. Hydroxypropyl methyl cellulose based hydrogel filled with the optimized FLB TRFs exhibited an improved ex vivo permeation when compared with the control FLB-loaded hydrogel. In addition, the optimized TRF-loaded hydrogel exhibited higher bioavailability and enhanced brain delivery relative to the control hydrogel following intranasal administration in Wistar rats. The results foreshadow the possible potential application of the proposed intranasal optimized FLB-TRF-loaded hydrogel to increase the bioavailability and nose-to-brain delivery of the drug.
... Hyaluronic acid (HA) is a polysaccharide frequently used in different biotechnological applications due to its natural, biodegradable, and nontoxic character which enables the formation of inert nanoparticles. In recent years, an extensive research on polysaccharide nanoparticles for several applications has been developed [9,10]. HA hydrogels have currently a large number of applications in biomaterials, including their use in tissue regeneration because of their high biocompatibility, or as drug delivery systems because their ability to retain liquids and bioactive compounds [11]. ...
... Afterwards, the organic fraction containing reverse micelles loaded with hyaluronic acid is Hyaluronic acid (HA) is a polysaccharide frequently used in different biotechnological applications due to its natural, biodegradable, and nontoxic character which enables the formation of inert nanoparticles. In recent years, an extensive research on polysaccharide nanoparticles for several applications has been developed [9,10]. HA hydrogels have currently a large number of applications in biomaterials, including their use in tissue regeneration because of their high biocompatibility, or as drug delivery systems because their ability to retain liquids and bioactive compounds [11]. ...
Conference Paper
Full-text available
Hydrogels (HG) are 3D networks of hydrophilic macromolecules linked by different “crosslinking points”, which have as a main advantage their capacity for the adsorption of large amounts of water without any apparent dissolution. This allows hydrogels to undergo reversible swelling–shrinking processes upon the modification of the environmental conditions (pH, ionic strength or temperature). This stimuli-responsiveness and their ability for entrapping in their interior different types of molecules makes hydrogels suitable platforms for drug delivery applications. Furthermore, HGs exhibit certain similarities to the extracellular tissue matrix and can be used as a support for cell proliferation and migration.
... 6,7 Supramolecular hydrogels are stimulus-responsive selfassembled intertwined fibrillar structures achieved through the cooperative effect of different non-covalent intermolecular interactions: hydrogen bonding, van der Waals, electrostatic, hydrophobic and aromatic interactions. [8][9][10][11][12][13][14][15][16][17][18] Their microdomains of solvent pockets afford physical-chemical similarity to the cell matrix and also allow the retention of nanoparticles, which tailor and modulate the hydrogel matrix structure and their mechanical, electrical, optical, and thermal properties. [10][11][12][13][14][15][16][17]19 Their hydrophobic and hydrophilic microdomains allow the loading and efficient transport of a wide variety of drugs, reducing side effects and enabling higher doses in therapy. ...
... [8][9][10][11][12][13][14][15][16][17][18] Their microdomains of solvent pockets afford physical-chemical similarity to the cell matrix and also allow the retention of nanoparticles, which tailor and modulate the hydrogel matrix structure and their mechanical, electrical, optical, and thermal properties. [10][11][12][13][14][15][16][17]19 Their hydrophobic and hydrophilic microdomains allow the loading and efficient transport of a wide variety of drugs, reducing side effects and enabling higher doses in therapy. 20 The combination of hydrogels with magnetic nanoparticles affords magnetogels, providing control and targeting of the nanosystem to a specific location through a magnetic field gradient and a higher therapeutic efficiency owing to the synergistic effect between magnetic hyperthermia and the enhanced drug release promoted by the application of an alternating magnetic field (AMF). ...
Article
Supramolecular hydrogels are highly promising for biomedical materials owing to the wide array of properties that can be tailored and modulated. The combination with plasmonic/magnetic nanoparticles into plasmonic magnetogels further improve its potential in biomedical applications, through the combination of complementary strategies, such as photothermia, magnetic hyperthermia, photodynamic therapy and magnetic-guided drug delivery. Here, a new dehydropeptide hydrogelator, Npx-L-Met-Z-ΔPhe-OH, was developed and combined with two different plasmonic/magnetic nanoparticles architectures: core/shell manganese ferrite/gold nanoparticles or gold-decorated manganese ferrite nanoparticles with ca. 55 nm and 45 nm size, respectively. The characterization of magnetogels were performed by HR-TEM, FTIR, circular dichorism and rheological assays. The gels were tested as nanocarriers for a model antitumor drug, the natural compound curcumin. The incorporation of the drug in magnetogel matrices was confirmed through fluorescence-based techniques (FRET, fluorescence anisotropy and quenching). The curcumin release profiles were studied with and without excitation of the gold plasmon band. The transport of curcumin from magnetogels towards biomembrane models (small unilamellar vesicles) was assessed by FRET between the fluorescent drug and the lipid probe Nile Red. The developed magnetogels showed promising results for photothermia and photo-triggered drug release. The magnetogels bearing gold-decorated nanoparticles showed the best photothermia properties, while the ones containing core/shell nanoparticles had the best photoinduced curcumin release.
... Self-assembled hydrogels have acquired a remarkable plethora of applications either in tissue engineering, in vivo imaging or drug delivery, owing to their high portion of water and physical-chemical similarity to the cellular matrix, both in composition and mechanical properties [12][13][14][15][16][17][18][19]. The gelation is achieved through the cooperative effect of different non-covalent intermolecular interactions: hydrogen bonding, van der Waals, electrostatic, hydrophobic and aromatic π-π interactions [7,9,[12][13][14][15]. ...
... The gelation is achieved through the cooperative effect of different non-covalent intermolecular interactions: hydrogen bonding, van der Waals, electrostatic, hydrophobic and aromatic π-π interactions [7,9,[12][13][14][15]. Therefore, the design, preparation and manipulation of the hydrogel must be cautious and rationally conceived since the gelation is affected by pH value, kinetics of pH drop, temperature, ionic force and structure amphiphilicity [7,9,[13][14][15][16][17][18][19][20]. ...
Article
Full-text available
Drug delivery nanosystems have been thriving in recent years as a promising application in therapeutics, seeking to solve the lack of specificity of conventional chemotherapy targeting and add further features such as enhanced magnetic resonance imaging, biosensing and hyperthermia. The combination of magnetic nanoparticles and hydrogels introduces a new generation of nanosystems, the magnetogels, which combine the advantages of both nanomaterials, apart from showing interesting properties unobtainable when both systems are separated. The presence of magnetic nanoparticles allows the control and targeting of the nanosystem to a specific location by an externally applied magnetic field gradient. Moreover, the application of an alternating magnetic field (AMF) not only allows therapy through hyperthermia, but also enhances drug delivery and chemotherapeutic desired effects, which combined with the hydrogel specificity, confer a high therapeutic efficiency. Therefore, the present review summarizes the magnetogels properties and critically discusses their current and recent biomedical applications, apart from an outlook on future goals and perspectives.
... One major hurdle for targeting a drug to the brain is the highly restrictive BBB, especially for non-invasive transport of drug to the brain. Oral delivery of drugs poses many issues including low bioavailability, slow absorption, hepatic first-pass metabolism, and gastrointestinal (GI) side effects (Salatin et al., 2016). Many of the current drug delivery strategies utilized in the above studies to enhance drug permeability through the BBB are invasive including intraventricular or intracerebral infusion of the drug. ...
Article
Full-text available
Chronic use of prescription opioids exacerbates risk and severity of ischemic stroke. Annually, 6 million people die from stroke worldwide and there are no neuroprotective or neurorestorative agents to improve stroke outcomes and promote recovery. Prescribed opioids such as morphine have been shown to alter tight junction protein expression, resulting in the disruption of the blood brain barrier (BBB), ultimately leading to stroke pathogenesis. Consequently, protection of the BBB has been proposed as a therapeutic strategy for ischemic stroke. This perspective addresses the deficiency in stroke pharmacological options and examines a novel application and repurposing of FDA-approved opioid antagonists as a prospective neuroprotective therapeutic strategy to minimize BBB damage, reduce stroke severity, and promote neural recovery. Future directions discuss potential drug design and delivery methods to enhance these novel therapeutic targets.
... In addition, they also play a significant role in controlling the nanostructures of the particles. Recently, a growing interest has been developed for water-soluble polymers for their application in physical and biological systems (Corot et al. 2006;Zhang et al. 2001); therefore, we used PVA for polymer nanocomposite preparation due to its easy process ability, high transmittance, biocompatibility, low toxicity, and lack of immunogenicity (Clemenson et al. 2007;Hamidi et al. 2008;Salatin et al. 2016). The treatment of AgNO 3 with the reducing agent hydrazine hydrate resulted in the reduction of silver ions (Ag + ) to silver particles (Ag 0 ), and PVA prevented the aggregation of formed meta-nanoparticles (Filippo et al. 2009;Patakfalvi et al. 2004). ...
Article
Full-text available
For developing an environmentally friendly, antibacterial, dehairing topical formulation, a β-keratinase enzyme (20.1 kDa) purified from Bacillus subtilis strain RM-01 was coupled to silver nanoparticles(AgNPs) of 8.0 ± 2.0 nm dimensions, prepared using poly(vinyl alcohol) matrix. The Plackett–Burman factorial design demonstrated that the pH of the buffer, amount of silver nanoparticles (Ag NPs), and concentration of β-keratinase enzyme play the most significant role in the Ag NP-enzyme-binding process. Biophysical techniques using scanning electron microscope, transmission electron microscope, X-ray diffraction, and Fourier-transform infrared spectroscopy (FT-IR) were used to characterize the free Ag NPs as well as AgNPs immobilized by β-keratinase. Binding of β-keratinase to Ag NPs resulted in a 5.6-fold increase in specific activity, a considerable increase in Vmax with a corresponding decrease in Km values towards keratin, and a significant improvement of the thermal and storage stabilities of immobilized enzyme compared to free enzyme. The enhanced antibacterial potency, dehairing activity, and organoleptic analysis of AgNPs immobilized with β-keratinase supports the industrial application of β-keratinase-immobilized Ag NPs in the pharmaceutical and cosmetic industries.
... The nanoparticles are located within the gel matrix itself or exterior Nano particulate systems such as incorporating Nano emulsion, liposome or Nano suspension into a gel matrix [18,19] . Nanogel can provide a homogenous distribution of nanoparticles with an enhanced thermodynamic activity of drug within gel formulation, with an ability to form aqueous solution with higher colloidal stability, an ability to accommodate macromolecules such as peptide and proteins, capability to load a higher drug quantity with no chemical reaction and a sustained drug delivery for prolonged time [20][21][22] . The object of present study was to formulated and evaluated insulin loaded thermo sensitive in situ nanogel for nasal delivery. ...
Article
Full-text available
The mucoadhesive gel formulations are helpful to prolong the residence time at the nasal absorption site and thereby facilitate the uptake of drug. The objective of the present study was to develop a thermo sensitive in Situ nanogel system based on chitosan and tripolyphosphate for nasal delivery of insulin. Nanogel containing insulin was prepared through an ionic gelation method. The concentration of the components was optimized during formulation development and then characterized in terms of Drug content, mucoadhesive strength, pH, Spreadability, and stability study and drug release behavior. The drug release results were fitted on five mathematical models to choose the model best describing the phenomenon. The in vitro release of insulin from gel network was observed spectrophotometrically which was good enough to maintain blood glucose level for 14 hour. Then the nano-formulation and insulin Sc injection as control were administered in the nasal cavity for rats and after 2, 4, 6, 8 and 10 hrs their blood glucose levels, serum insulin level analyzed for antidiabetic activity. The observed in vitro and in vivo results indicate that the proposed thermo sensitive in Situ gelling system has substantial potential as nasal delivery system for insulin.
... The formation of solvent pockets affords a means to retain nanoparticles that can be explored to tailor and modulate the hydrogel matrix physicochemical properties. [1][2][3][4][5][6][7][8][9][10][11][12] Magnetogels (hydrogels bearing magnetic nanoparticles) provide efficient loading and transport of drugs owing to the presence of both hydrophobic and hydrophilic microdomains, reducing side effects of chemotherapeutic drugs and enabling higher doses in therapy. 13 Moreover, the presence of magnetic nanoparticles provides control and targeting to a specific location through a magnetic field gradient and a higher therapeutic efficiency owing to the synergistic effect between magnetic hyperthermia and enhanced drug release. ...
Conference Paper
The combination of magnetic nanoparticles and hydrogels affords magnetogels, improving the manipulation of physicochemical properties and widening the range of applications, such as magnetic resonance imaging, biosensing, hyperthermia, drug delivery and as a template material. The introduction of plasmonic properties will synergistically enhance anticancer therapeutic strategies on the desired target through photothermia, drug release and photodynamic therapy. In this work, superparamagnetic manganese ferrite (MnFe2O4) nanoparticles coated with a gold shell were successfully incorporated into a self-assembled peptide-based hydrogel linked to a naproxen group, a lysine residue to stabilize the gold nanoparticle surface, and a dehydroamino acid that provides protease resistance. The new magnetogel was evaluated as nanocarrier for the model drug curcumin and the photothermia potential of the nanosystem was assessed. Microstructural properties of the hydrogels and magnetogels were studied by CD. Fluorescence-based techniques (fluorescence emission, quenching and FRET) were used to assess hydrogel physicochemical properties, incorporation of drugs and drug transport towards model membranes. The developed magnetic/plasmonic nanosystem exhibited promising results for photothermia application in multimodal cancer therapy, though future combination with other hydrogels will be required to improve its applicability.
... Advantages of PNPs as carriers for therapeutic agents include the ability to combine both imaging and therapy (theranostics), controlled release, improvement in the therapeutic index, and protection of drug molecules. PNPs have been prepared by synthetic and natural polymers such as sugars and proteins (Crucho and Barros, 2017; Salatin et al., 2016). PNPs can be either nanospheres or nanocapsules. ...
... This is in consistent with the reports from Dyer et al., 18 who indicated that insulin was less likely to be transported across the nasal membrane in nanoparticles form. The average size of pores in the nasal mucus is approximately 150 ± 50 nm, 38 and even 100 nm polystyrene nanoparticles coated with chitosan were only taken across the nasal membrane to a very low degree (<3% over 3 h). 39 Therefore, insulin tended to be absorbed across the nasal mucosa only after being released from the polyelectrolyte complexes. ...
Article
Nasal administration of insulin showed the attractive potential to improve the compliance of diabetic patients and alleviate mild cognitive impairment of Alzheimer's patients. However, the nasal absorption of insulin was not ideal, limiting its therapeutic effect in clinic. This study was to explore the potential of glyceryl monocaprylate-modified chitosan (CS-GMC) on the intranasal absorption of insulin via in vivo pharmacodynamic experiment in conscious rats. It was demonstrated that the absorption-enhancing effect of CS-GMC depended on the existing state of insulin in the formulation, substitution degree of GMC on chitosan and concentration of CS-GMC. Better insulin absorption was achieved when insulin existed in molecular form compared with that in polyelectrolyte complexes. CS-GMC with substitution degree 12% (CS-GMC 12%) was a preferred absorption enhancer, and its absorption enhancing effect increased linearly with the increment of its concentration in the range investigated. Compared with chitosan of the same concentration, CS-GMC12% showed remarkably enhanced and prolonged therapeutic effect up to at least 5 h under the concentration of 0.6% (w/v). CS-GMC12% showed almost no ciliotoxicity to the nasal cilia up to concentration 1.0% (w/v). In conclusion, CS-GMC was a promising absorption enhancer to improve the intranasal absorption of insulin.
... By contrast, the branched amylose-coated nanogel was stable due to the steric hindrance [35]. Numerous reports on physical self-assembly of nanogels in the field of drug delivery have also been published [36][37][38][39]. Core-shell nanogel [42,43] 4 ...
Article
Nanogels are three-dimensional nanoscale networks formed by physically or chemically crosslinking polymers. Nanogels have been explored as drug delivery systems due to their advantageous properties, such as biocompatibility, high stability, tunable particle size, drug loading capacity, and possible modification of the surface for active targeting by attaching ligands that recognize cognate receptors on the target cells or tissues. Nanogels can be designed to be stimulus responsive, and react to internal or external stimuli such as pH, temperature, light and redox, thus resulting in the controlled release of loaded drugs. This “smart” targeting ability prevents drug accumulation in non-target tissues and minimizes the side effects of the drug. This review aims to provide an introduction to nanogels, their preparation methods,and to discuss the design of various stimulus-responsive nanogels that are able to provide controlled drug release in response to particular stimuli.
... Agarose is a polysaccharide frequently used in different biotechnological applications due to its natural, biodegradable, and nontoxic character which enables the formation of inert nanoparticles. In recent years, an extensive research on polysaccharide nanoparticles for several applications has been developed [23,24]. Among such polysaccharides, the use of agarose for the fabrication of nanoparticles is widely extended [25,26]. ...
Article
Full-text available
In this work, monodisperse agarose gel nanoparticles were prepared using a W/O microemulsion as a template to control the size of the obtained particles. The combination of this template method with a temperature-induced gelling and a solvent exchange methodology has allowed preparing stable aqueous dispersions of monodisperse agarose gel nanoparticles in water. The average size, measured as an apparent hydrodynamic diameter, of the obtained particles was around 150 nm. The ability of the obtained hydrogel particles for the encapsulation and release of a synthetic insecticide (azamethiphos) was tested. The results evidence that the insecticide molecules encapsulated in the fabricated nanoparticles are released following a diffusion-controlled mechanism. These results combined with the biodegradability of the agarose provide the bases for the design of a new vector with application in the control of parasites in water reservoirs.
... The introduction of recognizable molecules on the surface of the particle gives it the ability to recognize target cells, and also permits the gradual degradation of the polymer within the cell. It is therefore widely used in drug development and delivery [20,21]. Hemostasis material, medical dressing, hydrogel, drug delivery carrier, gene transfer [22] Biocompatibility, antimicrobial, innocuous, easily degradable, adsorbability, film formation [23][24][25][26][27] Poor spinnability, poor strength, low water-solubility [23,25] Starch Hemostasis material, tissue-engineered scaffold, drug delivery carrier, bone repair material [28,29] Extensive sources, low price, degradation products safe and non-toxic, non-antigenic [28,30] Poor mechanical properties, resistance to water, poor blocking performance [28,30] Alginate Pharmaceutical excipient, pepcid complete, medical dressing [31][32][33][34][35] Hypotoxicity, biocompatibility, suppresses tumor growth, enhances immunity [31][32][33][34][35] Bad biodegradability, cell attachment poor [31][32][33][34][35] Cellulose Pharmaceutical adjuvant [28] Extensive sources, low price [28] Rare adverse reactions [28] ...
Article
Nanotechnology plays a significant role in drug development. As carriers, polymeric nanoparticles can deliver vaccine antigens, proteins, and drugs to the desired site of action. Polymeric nanoparticles with lower cytotoxicity can protect the delivered antigens or drugs from degradation under unfavorable conditions via a mucosal administration route; further, the uptake of nanoparticles by antigen-presenting cells can increase and induce potent immune responses. Additionally, nanomaterials are widely used in vaccine delivery systems because nanomaterials can make the vaccine antigen long-acting. This review focuses on some biodegradable polymer materials such as natural polymeric nanomaterials, chemically synthesized polymer materials, and biosynthesized polymeric materials, and points out the advantages and the direction of research on degradable polymeric materials. The application and future perspectives of polymeric materials as delivery carriers and vaccine adjuvants in the field of drugs and vaccines are presented. With the increase of knowledge and fundamental understandings of polymer-based nanomaterials, means of integrating some other attractive properties, such as slow release, target delivery, and alternative administration methods and delivery pathways are feasible. Polymer-based nanomaterials have great potential for the development of novel vaccines and drug systems for certain needs, including single-dose and needle-free deliveries of vaccine antigens and drugs in the future.
... A hydrogel is a type of gel that swells in water, and is made up of a threedimensional crosslinked configuration of amphiphilic or hydrophilic polyionic polymers. Hydrogel-forming vesicles in the nanometer size (1À1000 nm) are often termed as nanogels, or hydrogel nanoparticles [127]. Hydrogels could be designed to show phase transition (and therefore cargo release) in response to temperature, pH, molecular species, and ionic strength. ...
Chapter
Vaccination is a cost-effective approach to prevent, treat, and eradicate infectious diseases and cancer. Classical whole-organism vaccines may have several pitfalls such as the potential risk of inducing autoimmune and/or allergic responses. Synthetic peptide-based vaccines are an alternative solution to overcome the disadvantages associated with classical vaccines. Peptide-based vaccines are built of defined, small-peptide antigens engineered to induce the desired immune response. However, these peptides are poorly immunogenic and need to be delivered with additional immune-stimulating agents such as adjuvants or particulate delivery systems/carriers. Herein, we discuss the development of peptide-based vaccines with a special focus on epitope identification, adjuvant discovery, and delivery system selection.
... Besides, the engineered PVP nanogels have a well-controlled hydrodynamic size distribution (ca. 70 ± 20 nm) in a range that should ensure their pass through the nasal mucosal barrier [50]. The high hydrophilicity, soft consistency and "open" molecular structure altogether makes them perfect candidates for conjugation of large biomolecules and their protection from enzymatic degradation. ...
Article
Recent evidences suggest that insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD). Due to the presence of the Blood Brain Barrier, a suitable carrier and an appropriate route of administration are required to increase the efficacy and safety of the treatment. Here, poly(N-vinyl pyrrolidone)-based nanogels (NG), synthetized by e-beam irradiation, alone and with covalently attached insulin (NG-In) were characterized for biocompatibility and brain delivery features in a mouse model. Preliminarily, the biodistribution of the "empty" nanocarrier after intraperitoneal (i.p.) injection was investigated by using a fluorescent-labeled NG. By fluorescence spectroscopy, SEM and dynamic light scattering analyses we established that urine clearance occurs in 24h. Histological liver and kidneys inspections indicated that no morphological alterations of tissues occurred and no immunological response was activated after NG injection. Furthermore, after administration of the insulin-conjugated nanogels (NG-In) through the intranasal route (i.n.) no alteration or immunogenic response of the nasal mucosa was observed, suggesting that the formulation is well tolerated in mouse. Moreover, an enhancement of NG-In delivery to the different brain areas and of its biological activity, measured as Akt activation levels, with reference to free insulin administration was demonstrated. Taken together, these results indicate that the synthesized NG-In enhances brain insulin delivery upon i.n. administration and strongly encourage its further evaluation as therapeutic agent against some neurodegenerative diseases.
... Nanoparticles have the ability to enhance nasal delivery of vaccines, as compared to conventional formulations. Hydrogel nanosystems have muco-adhesive properties that maximize residence time and hence increase the period of contact with the nasal mucosa, enhancing vaccine absorption [94]. Marques Neto et al. [95] have reviewed the characteristics of metal NPs that could facilitate induction of a cellular immune response, particularly T-helper 1 and T-helper 17, and their potential functions as adjuvants for subunit vaccines. ...
Chapter
During the last decade, there have been enormous developments in utilizing the power of nanotechnology in various fields including biomedical sciences. The most important biomedical applications of nanoparticles (NPs) are in disease diagnosis and treatment. Functionalized NPs possess unique properties as contrast agents for dual and even triple modal imaging. The potential of these new generation NPs in targeted drug delivery has revolutionized safe and effective pharmacotherapies for complex diseases. One more step ahead, theranostic NPs are equipped with dual capabilities for disease diagnosis as well as treatment. Specifically, designed NPs have also been utilized to improve the delivery and efficiency of different vaccines, including their application in cancer immunotherapy. This chapter provides an overview of the biomedical applications of NPs and recent advancements in this area on the basis of current research.
... 13 Moreover, hydrogel nanoparticles as a combination of a hydrogel system and nanoparticles and also due to their superior features, such as the option of the use of natural or synthetic polymers for the gel preparation and tendency to form aqueous solutions, are the ideal candidates for different applications. 14 The development of biodegradable, antibacterial polymeric nanosystems has been promising as the polymeric nanosystems enhanced bacterial recognition, and antibacterial nanosystems with enhanced biocompatibility can be envisaged for potential clinical applications. 15 Versatile methodologies for fabricating nanohydrogel, such as emulsion polymerization, nanoprecipitation, solvent evaporation, solvent deposition of natural polymers, inotropic gelation and the emulsification-diffusion method, have been proposed in various studies. ...
Article
The goal of this paper was to study some chemical and physical effects of chitosan nano-hydrogels containing Rhus coriaria on cotton fabric. The finished fabrics showed antimicrobial effects against two pathogenic microorganisms, namely Staphylococcus aureus and Escherichia coli, and the particle size, as well as the effect of encapsulating sumac extract in chitosan nano-hydrogel on some physical and visual characteristics of fabrics, are then confirmed by using various methods, including antimicrobial testing, scanning electron microscopy, Fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy. The encapsulation efficiency and release behavior of the samples are also studied. The as-prepared samples with higher sumac content have more ultraviolet (UV) absorbing activity (about 52%) than the un-treated sample, as well as excellent washing fastness and antimicrobial properties after five washing cycles. More specifically, these methods indicated negligible changes in color and thickness of treated cotton fabrics. Finally, the application of cotton fabric along with the synthesis of chitosan nano-hydrogel and sumac loading introduced a novel cotton fabric with high antimicrobial properties, washing fastness and UV protection property.
... Table 4 lists many research publications concentrating on various biomaterials in vaccine administration. The capacity of these materials to self-assemble around antigens under aqueous circumstances, as well as their accessibility for various and site-specific post-synthetic alterations, is a considerable benefit [145][146][147]. The ability to alter formulations far off nano or microparticles or solid implants is one advantage of hybrid or blended biomaterials. ...
... 6 The hydrophilic polymeric networks of hydrogels can retain water without losing their inner structure, and they can also be used as carriers for drug and protein delivery. [7][8][9] Gellan gum (GG) hydrogel is a biodegradable polysaccharide with high cytocompatibility and has been approved by the United States Food and Drug Administration as a biomaterial. [10][11][12] Numerous studies on the application of GG hydrogels have been carried out in tissue engineering, including studies on brain tissue engineering and cartilage and intervertebral disc applications. ...
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Objective: Tissue engineering is a promising strategy for repair of large bone defect. However, the immune system reactions to biological scaffold are increasingly being recognized as a crucial factor influencing regeneration efficacy. In this study, a bone-bioactive hydrogel bead loaded with interleukin-4 (IL-4) was used to regulate macrophages polarization and accelerate bone regeneration. Methods: IL-4-loaded calcium-enriched gellan gum (Ca-GG + IL-4) hydrogel beads were synthesised. And the effect on cell behaviour was detected. Furthermore, the effect of the Ca-GG + IL-4 hydrogel bead on macrophage polarization and the effect of macrophage polarization on bone mesenchymal stem cells (BMSCs) apoptosis and osteogenic differentiation were evaluated in vitro and in vivo. Results: BMSCs were able to survive in the hydrogel regardless of whether IL-4 was incorporated. Immunofluorescence staining and qPCR results revealed that Ca-GG + IL-4 hydrogel bead could promote M2 macrophage polarization and increase transforming growth factor (TGF)-β1 expression level, which activates the TGF-β1/Smad signalling pathway in BMSCs and promotes osteogenic differentiation. Moreover, immunohistochemical analysis demonstrated Ca-GG + IL-4 hydrogel bead could promote M2 macrophage polarization and reduce cell apoptosis in vivo. In addition, micro-CT and immunohistochemical analysis at 12 weeks post-surgery showed that Ca-GG + IL-4 hydrogel bead could achieve superior bone defect repair efficacy in vivo. Conclusions: The Ca-GG + IL-4 hydrogel bead effectively promoted bone defect regeneration via regulating macrophage polarization, reducing cell apoptosis and promoting BMSCs osteogenesis through TGF-β1/Smad pathway. Therefore, it is a promising strategy for repair of bone defect.
... In addition, it also has the potential to carry drugs directly across the blood-brain barrier through olfactory and trigeminal nerve cells [247]. Based on these findings, hydrogel-based formulations have been developed for delivering drugs through the nose for the treatment of local diseases, intranasal vaccinations, the systemic delivery of drugs, and the direct delivery of therapeutic molecules to the brain [248]. ...
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Recently, hydrogels have been investigated for the controlled release of bioactive molecules, such as for living cell encapsulation and matrices. Due to their remote controllability and quick response, hydrogels are widely used for various applications, including drug delivery. The rate and extent to which the drugs reach their targets are highly dependent on the carriers used in drug delivery systems; therefore the demand for biodegradable and intelligent carriers is progressively increasing. The biodegradable nature of hydrogel has created much interest for its use in drug delivery systems. The first part of this review focuses on emerging fabrication strategies of hydrogel, including physical and chemical cross-linking, as well as radiation cross-linking. The second part describes the applications of hydrogels in various fields, including drug delivery systems. In the end, an overview of the application of hydrogels prepared from several natural polymers in drug delivery is presented.
... NPs and nanocomposites are widely used for the controlled release of active cargo at a desired time and location. Polymer-based NPs are usually 10-500 nm in diameter, with bioactive materials internalized through dissolving, wrapping, adsorption, and/or adhesion on the surface or inside the particles [47]. ...
Chapter
Vaccination renders protection against pathogens via stimulation of the body’s natural immune responses. Classical vaccines that utilize whole organisms or proteins have several disadvantages, such as induction of undesired immune responses, poor stability, and manufacturing difficulties. The use of minimal immunogenic pathogen components as vaccine antigens, i.e., peptides, can greatly reduce these shortcomings. However, subunit antigens require a specific delivery system and immune adjuvant to increase their efficacy. Recently, nanotechnology has been extensively utilized to address this issue. Nanotechnology-based formulation of peptide vaccines can boost immunogenicity and efficiently induce cellular and humoral immune responses. This chapter outlines the recent developments and advances of nano-sized delivery platforms for peptide antigens, including nanoparticles composed of polymers, peptides, lipids, and inorganic materials.
... Additionally, the one-end open mouth structure of the nanotubes simplifies their mountings. The hydrogels or "nano jelly" offers simpler synthetic methods with relatively high potential for drug loading, which was also well applicable for topical delivery [318]. These hydrophilic polymer nets are crosslinked 3D networks and are swellable in an aqueous environment [319]. ...
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Full-text available
This review focuses on nano-structured delivery devices prepared from biodegradable and biocompatible natural and synthetic polymers, organic raw materials, metals, metal oxides, and their other compounds that culminated in the preparation of various nano-entities depending on the preparative techniques, and starting raw materials’ utilizations. Many nanoparticles (NPs) made of polymeric, metallic, magnetic, and non-magnetic origins, liposomes, hydrogels, dendrimers, and other carbon-based nano-entities have been produced. Developments in nanomaterial substrate and end products’ design, structural specifications, preparative strategies, chemo-biological interfacing to involve the biosystems interactions, surface functionalization, and on-site biomolecular and physiology-mediated target-specific delivery concepts, examples, and applications are outlined. The inherent toxicity, and safety of the design concepts in nanomaterial preparation, and their applications in biomedical fields, especially to the organs, cellular and sub-cellular deliveries are deliberated. Bioapplications, the therapeutic delivery modules’ pharmacokinetics and medicinal values, nanopharmaceutical designs, and their contributions as nano-entities in the healthcare biotechnology of drug delivery domains have also been discussed. The importance of site-specific triggers in nano-scale deliveries, the inherent and induced structural specifications of numerous nanomaterial entities belonging to NPs, nano-scale composites, nano-conjugates, and other nano-devices of organic and inorganic origins, near biological systems are detailed. Modifications that provide nano-deliveries of their intrinsic therapeutic actions, through structural and physicochemical characteristics modifications, and the proven success of various nano-delivery devices and currently available commercial nanomedicinal and nanopharmaceutical products are also provided.
... Hydrogel NPs are 3-D polymer structures utilized for encapsulation and delivery of drugs. These edifices swell in aquatic or organic settings, as it absorbs more fluid (Salatin et al., 2016). In addition to hydrogel ensnarement, the construction of a three-dimensional hydrogel network (where the nanoparticles are used directly as a crosslinking agent) also provides another way of assembling nanoparticles to achieve hydrogel-like properties (e.g. ...
Chapter
The rapid growth of nanotechnology towards the development of nanomedicines has improved cancer treatment. Nanomedicine provides the opportunity to implement complex and targeted multifunctional strategies. Today, nanoparticles (NPs) have many uses in a number of scientific fields. In recent years, it has been repeatedly reported that NPs hold a significant place in the regulation of modern medicine by implementing a varying number of clinical approaches like drug carrying substances, genetic material delivery to tumors, as well as in radiography as a contrast media agent. Various nanomaterials based on organic, inorganic, lipid or glycan compounds, and synthetic polymers have been used to develop and improve new cancer treatments. In this chapter, the authors discussed the role of NPs in cancer treatment among various anticancer drug delivery methods.
... To reduce the rate of release, there are various strategies that can be followed which alter the interaction between drug and matrix or increase the diffusion barrier to increase the drug delivery rate of the hydrogel. Possible strategies that can be used are dry hydrogel interaction, physical interaction using charges, covalent bonding, gel network engineering where microstructure of hydrogel is modified by increasing the percentage of cross-linking monomer that incorporates into the gel, and interpenetrating polymer network [75]. ...
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The hydrogels are three-dimensional, water-swollen structures composed mainly of hydrophilic homo-polymers or copolymers utilized in various fields. This review explains in detail about the various methods used in the synthesis of hydrogel, their loading mechanism, their swelling index, their chemical and physical properties, and also comparative analysis between chemo-drug and drug-entrapped hydrogel. In this, we will also discuss various applications of hydrogel, which aid in treating diseases, like Alzheimer’s disease, Parkinson disease, etc., using modified drug delivery mechanism. Though these diseases have various methods of treatment, they have a common ground and that is the need for definite amounts and a prolonged release of drugs which will be possible with the aid of hydrogels. The use of hydrogel is believed to be an upgrade in the medical field, and its involvement in treatments is considered to be sincerely encouraged.
... Vaccines can be administered into a patient without using a conventional needle, thereby reducing patients' concerns and fear about the use of needles. It would also help in reducing the risk of bloodborne infections, such as human immunodeficiency virus (HIV), and ultimately increasing the patient compliance ( Figure 2) (Salatin et al., 2016). In terms of prophylactic and therapeutic capacities, vaccines can induce mucosal immune responses against various diseases even cancer. ...
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Drug delivery using oral route is the most popular, convenient, safest and least expensive approach. It includes oral transmucosal delivery of bioactive compounds as the mucosal cavity offers an intriguing approach for systemic drug distribution. Owing to the dense vascular architecture and high blood flow, oral mucosal layers are easily permeable and can be an ideal site for drug administration. Recently, the transmucosal route is being investigated for other therapeutic candidates such as vaccines for their efficient delivery. Vaccines have the potential to trigger immune reactions and can act as both prophylactic and therapeutic conduit to a variety of diseases. Administration of vaccines using transmucosal route offers multiple advantages, the most important one being the needle-free (non-invasive) delivery. Development of needle-free devices are the most recent and pioneering breakthrough in the delivery of drugs and vaccines, enabling patients to avoid needles, reducing anxiety, pain and fear as well as improving compliance. Oral, nasal and aerosol vaccination is a novel immunization approach that utilizes a nanocarrier to administer the vaccine. Nanocarriers improve the bioavailability and serve as adjuvants to elicit a stronger immune response, resulting in increased effectiveness of vaccination. Drugs and vaccines with lower penetration abilities can also be delivered transmucosally while maintaining their biological function. The development of micro/nanocarriers for transmucosal delivery of macromolecules, vaccines and other substances is currently drawing much attention and a number of studies were performed recently. This comprehensive review is aimed to summarize the most recent investigations on needle-free and non-invasive approaches for the delivery of vaccines using oral transmucosal route, their strengths and associated challenges. The oral transmucosal vaccine delivery by nanocarriers is the most upcoming advancement in efficient vaccine delivery and this review would help further research and trials in this field.
... Several research reports focusing on these biomaterials in vaccine delivery are listed in Table 3. A significant advantage of these materials is their ability to self-assemble around antigens under aqueous conditions and their availability for multiple and site-specific post-synthetic modifications (Corthésy & Bioley, 2018;Salatin et al., 2016;N. Wang, Chen, & Wang, 2019). ...
Article
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Vaccines are considered one of the most significant medical advancements in human history, as they have prevented hundreds of millions of deaths since their discovery; however, modern travel permits disease spread at unprecedented rates, and vaccine shortcomings like thermal sensitivity and required booster shots have been made evident by the COVID-19 pandemic. Approaches to overcoming these issues appear promising via the integration of vaccine technology with biomaterials, which offer sustained-release properties and preserve proteins, prevent conformational changes, and enable storage at room temperature. Sustained release and thermal stabilization of therapeutic biomacromolecules is an emerging area that integrates material science, chemistry, immunology, nanotechnology, and pathology to investigate different biocompatible materials. Biomaterials, including natural sugar polymers, synthetic polyesters produced from biologically derived monomers, hydrogel blends, protein–polymer blends, and metal–organic frameworks, have emerged as early players in the field. This overview will focus on significant advances of sustained release biomaterial in the context of vaccines against infectious disease and the progress made towards thermally stable “single-shot” formulations. This article is categorized under: • Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Abstract Most vaccines require refrigeration and many need multiple-injections to exert their full therapeutic potential. In this overview, we discuss how combining vaccines with biomaterials are poised to help overcome both of these issues.
... Its advantageous properties, including muco-adhesion, biocompatibility, and targetability to HA receptors (CD44), which are highly expressed in various tumor and stem cells, support intranasal application. The coating of liposomes with HA increases their negative zeta potential due to the addition of the negative carboxylate residue of HA on the surface of the liposomes, thereby increasing directly their stability [9]. A novel bottom-up method of preparation called the direct pouring method (DPM) is a modified form of the solvent injection and emulsification method but quite feasible as it avoids the use of extra size reduction, extrusion, or filtration techniques. ...
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The present study aimed to develop n-propyl gallate (PG)-encapsulated liposomes through a novel direct pouring method using the quality-by-design (QbD) approach. A further aim was to coat liposomes with hyaluronic acid (HA) to improve the stability of the formulation in nasal mucosa. The QbD method was used for the determination of critical quality attributes in the formulation of PG-loaded liposomes coated with HA. The optimized formulation was determined by applying the Box–Behnken design to investigate the effect of composition and process variables on particle size, polydispersity index (PDI), and zeta potential. Physiochemical characterization, in vitro release, and permeability tests, as well as accelerated stability studies, were performed with the optimized liposomal formulation. The optimized formulation resulted in 90 ± 3.6% encapsulation efficiency, 167.9 ± 3.5 nm average hydrodynamic diameter, 0.129 ± 0.002 PDI, and −33.9 ± 4.5 zeta potential. Coated liposomes showed significantly improved properties in 24 h in an in vitro release test (>60%), in vitro permeability measurement (420 µg/cm2) within 60 min, and also in accelerated stability studies compared to uncoated liposomes. A hydrogen-peroxide-scavenging assay showed improved stability of PG-containing liposomes. It can be concluded that the optimization of PG-encapsulated liposomes coated with HA has great potential for targeting several brain diseases.
... Its advantageous properties, including muco-adhesion, biocompatibility, and targetability to HA receptors (CD44), which are highly expressed in various tumor and stem cells, support intranasal application. The coating of liposomes with HA increases their negative zeta potential due to the addition of the negative carboxylate residue of HA on the surface of the liposomes, thereby increasing directly their stability [9]. A novel bottom-up method of preparation called the direct pouring method (DPM) is a modified form of the solvent injection and emulsification method but quite feasible as it avoids the use of extra size reduction, extrusion, or filtration techniques. ...
Article
Full-text available
The present study aimed to develop n-propyl gallate (PG)-encapsulated liposomes through a novel direct pouring method using the quality-by-design (QbD) approach. A further aim was to coat liposomes with hyaluronic acid (HA) to improve the stability of the formulation in nasal mucosa.The QbD method was used for the determination of critical quality attributes in the formulation of PG-loaded liposomes coated with HA. The optimized formulation was determined by applying the Box–Behnken design to investigate the effect of composition and process variables on particle size, polydispersity index (PDI), and zeta potential. Physiochemical characterization, in vitro release, and permeability tests, as well as accelerated stability studies, were performed with the optimized liposomal formulation. The optimized formulation resulted in 90 ± 3.6% encapsulation efficiency, 167.9 ± 3.5 nm average hydrodynamic diameter, 0.129 ± 0.002 PDI, and −33.9 ± 4.5 zeta potential. Coated liposomes showed significantly improved properties in 24 h in an in vitro release test (>60%), in vitro permeability measurement (420 µg/cm2) within 60 min, and also in accelerated stability studies compared to uncoated liposomes. A hydrogen-peroxide-scavenging assay showed improved stability of PG-containing liposomes. It can be concluded that the optimization of PG-encapsulated liposomes coated with HA has great potential for targeting several brain diseases.
... Additionally, the one-end open mouth structure of the nanotubes simplifies their mountings. The hydrogels or "nano jelly" offers simpler synthetic methods with relatively high potential for drug loading, which was also well applicable for topical delivery [318]. These hydrophilic polymer nets are crosslinked 3D networks and are swellable in an aqueous environment [319]. ...
Article
Full-text available
This review focuses on nano-structured delivery devices prepared from biodegradable and biocompatible natural and synthetic polymers, organic raw materials, metals, metal oxides, and their other compounds that culminated in the preparation of various nano-entities depending on the preparative techniques, and starting raw materials' utilizations. Many nanoparticles (NPs) made of polymeric, metallic, magnetic, and non-magnetic origins, liposomes, hydrogels, dendrimers, and other carbon-based nano-entities have been produced. Developments in nano-material substrate and end products' design, structural specifications, preparative strategies, chemo-biological interfacing to involve the biosystems interactions, surface functionalization, and on-site biomolecular and physiology mediated target-specific delivery concepts, examples , and applications are outlined. The inherent toxicity, and safety of the design concepts in nanomaterial preparation , and their applications in biomedical fields, especially to the organs, cellular and sub-cellular deliveries are deliberated. Bioapplications, the therapeutic delivery modules' pharmacokinetics and medicinal values, nanopharmaceu-tical designs, and their contributions as nano-entities in the healthcare biotechnology of drug delivery domains have also been discussed. The importance of site-specific triggers in nano-scale deliveries, the inherent and induced structural specifications of numerous nanomaterial entities belonging to NPs, nano-scale composites, nano-conjugates, and other nano-devices of organic and inorganic origins, near biological systems are detailed. Modifications that provide nano-deliveries of their intrinsic therapeutic actions, through structural and physicochemical characteristics modifications, and the proven success of various nano-delivery
Article
Selegiline hydrochloride (SL) is chosen as an adjunct for the control of clinical signs of Parkinsonian patients. The aim of the present work is to develop and optimize thermosensitive gels using Pluronic (F-127) for enhancing transport of SL into the brain through the nasal route. SL gels were prepared using a cold method and the Box-Behnken experimental design methodology. Drug (SL), gelling agent (F-127) and emulsifier (Propylene glycol, PG) were selected as independent variables while the gelation temperature, gel strength, pH, gel content, and gel erosion were considered as dependent variables. For further understanding of the interaction between the various variables, contour plots and surface plots were also applied. Selected formulations, like S10 (contain 25 mg SL, 20 g F-127, and 1 g PG) and S14 (contain 50 mg SL, 18 g F-127 and 1 g PG), had a clear appearance in the sol form, with gelling temperature of the nasal gel ranging between 33 and 34, respectively. The gel strength of the formulations varied from 4.67 and 0.68 mm and the drug content was 100%. The pH of the formulations ranged between 6.71 and 7.11. Detachment force was acceptable (63.69-244.16 N/cm2) to provide prolonged adhesion. In vitro, drug release studies showed that the prepared formulations could release SL for up to 8 h. Permeation flux for the S10 gel was 0.0002 mg/min/cm². Results demonstrated the potential use of SL gels to can enhance the therapeutic effect of SL through the intranasal administration.
Chapter
Nanotherapeutics research has been rising steadily in interdisciplinary core area for the development of targeted drug delivery system. The poor gastrointestinal stability, low bioavailability, poor transport behavior limitations are overcome by nanodrug delivery system. The design of an effective drug delivery system depends on the particle size, functional moieties, textural characteristics (surface area, pore size, and pore volume), targeting ligand, cleavable and non-cleavable linker, drug sensitivity to environment stimuli, etc. The functionalization of drugs over nanocarriers needs to improve the stability of drug components, increase the bioavailability, reduce metabolization and excretion. Different types of nanocarriers broadly based on structured silica, carbon, polymers, liposome, metal nanoparticles, gel, nanocage, clay, and viral carriers have been developed for drug delivery system. Infectious diseases are rising globally prompting the need for an advanced drug delivery to overcome the present challenges to solutions. One best option is to utilize the advantages of individual components in mutual nanocomposites. Porous silica and carbon nanocarriers are advantageous with high textural uniformity, non-toxic with high drug loading capabilities. However, several linkers and polymeric wrappings are required for developing a stimuli responsive drug delivery system. Polymeric nanogels are attractive drug delivery options for treating lung infections. However, the hydrogels are affected by mechanical based stress leading to disorientation of porous network by ruptures. Developing a hybrid variants involving silica/hydrogel and carbon/hydrogel nanocomposites could be interesting due to increased stability with similar tissue morphological features that are favorable for microenvironment. Nanocomposites design based on the pharmacological metals, recognition receptors, green nanoparticles, virus mimicking structures, and polyphenols can improve the delivery of vaccines, peptide/antiviral drugs.
Article
Intranasal administration of pharmaceutical compounds is gaining considerable attention as an alternative route for localized/systemic drug delivery. However, insufficient therapeutic efficacy of drugs via this route seems to be a major challenge for development of de novo intranasal formulations. This shortcoming can be overcome by simultaneous utilization of a nanoparticulate delivery system with a polymeric gel network. Therefore, the main aim of the present study was to develop erodible in-situ gel forming systems of poloxamer 407(®) (P407) as a promising platform, capable of prolonging rivastigmine hydrogen tartrate (RHT) release from the embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). PLGA NPs containing RHT were formulated and characterized, then were embedded in P407 gel forming matrix and analyzed in terms of viscosity, stability, gelation temperature, loading efficiency and mucoahesive behavior. The cytotoxicity of NPs was evaluated on A549 cell line using MTT assay. Cellular uptake of the NPs was also measured by means of fluorescence microcopy and flow cytometry analyses. The formulations were finally evaluated for their permeability across sheep nasal mucosa. A linear dependence of sol-gel temperature (Tsol-gel) on the P407 concentration was observed, and a P407 content of 18% was selected. The loading efficiencies of formulations were found to be around 100.22-104.31%. The RHT-loaded NPs showed a suitable cytocompatibility on A549 cells with a time-dependent increase in cellular uptake. Besides, nanocomposites showed higher amounts of drug permeation through nasal sheep mucosa than plain drug gel. Taken all, it is concluded that the formulated nanocomposites may be considered as useful drug delivery systems for the nasal delivery of RHT with enhanced therapeutic efficacy.
Article
Realization of the immense potential of nanomaterials for biomedical applications will require a thorough understanding of how they interact with cells, tissues, and organs. There is evidence that, depending on their physicochemical properties and subsequent interactions, nanomaterials are indeed taken up by cells. However, the subsequent release and/or intracellular degradation of the materials, transfer to other cells, and/or translocation across tissue barriers are still poorly understood. The involvement of these cellular clearance mechanisms strongly influences the long-term fate of used nanomaterials, especially if one also considers repeated exposure. Several nanomaterials, such as liposomes and iron oxide, gold, or silica nanoparticles, are already approved by the American Food and Drug Administration for clinical trials; however, there is still a huge gap of knowledge concerning their fate in the body. Herein, clinically relevant nanomaterials, their possible modes of exposure, as well as the biological barriers they must overcome to be effective are reviewed. Furthermore, the biodistribution and kinetics of nanomaterials and their modes of clearance are discussed, knowledge of the long-term fates of a selection of nanomaterials is summarized, and the critical points that must be considered for future research are addressed.
Article
Armodafinil is typically used in clinical practice to maintain cognition and wakefulness in patients suffering from sleep deprivation. However, its poor water solubility and large dosage limit its effective application. Herein, we formulated armodafinil in a nanocrystal hydrogel (NCsG) with appropriate fluidity and viscosity, capable of rapidly dissolving after staying in the nasal cavity for >4 h and then penetrating the mucosa as quickly as possible in vitro. We found that armodafinil NCsG was biologically safe, as it had no visible ciliary toxicity, as well as extremely stable due to the existence of intermolecular hydrogen-bonding forces. Nasal administration of armodafinil NCsG proved to be more efficient and targeted than oral administration due to its preferential absorption in plasma and more-concentrated distribution in the brain. In addition, compared with the model group, sleep-deprived rats treated with NCsG undergoing Morris water maze (MWM) behavioral experiments had shorter escape latency and much more shuttle times across the platform. Meanwhile, in the open-field test (OFT), these same rats had longer periods of movement in the center, longer time spent upright, and lower anxiety, which clearly demonstrated improved cognitive awareness and wakefulness after intranasal administration. Moreover, we speculated that armodafinil NCsG had a protective effect on hippocampal neurons in Cortical Area 1 (CA1), which is closely related to cognitive function, by upregulating brain-derived neurotrophic factor (BDNF) protein expression. Consequently, the intranasal administration of armodafinil NCsG could serve as a promising integrated-control measure for sleep deprivation.
Article
We present an antibacterial polymersome-hydrogel composite that combined advantages of both antimicrobial peptides and antibiotics. The polymersomes are self-assembled from poly(ε-caprolactone)-block-poly(lysine-stat-phenylalanine) [PCL-b-P(Lys-stat-Phe)], exhibiting long-acting intrinsic antibacterial capabilities against both Gram-positive and Gram-negative bacteria. In addition, Penicillin is encapsulated into polymersomes, showing quick and enhanced antibacterial activities. Furthermore, a dynamic hydrogel network is prepared based on the Schiff base linkages between the aldehyde groups of the dibenzaldehyde-functionalized PEG (DF-PEG) and the amino groups of the chitosan. In the mean time, the penicillin-loaded polymersomes are grafted into the hydrogel networks by Schiff base linkages to afford the polymersome-hydrogel composites, which exhibit two-stage antibacterial behavior: (1) Penicillin can be released from the hydrogel networks for quick antibacterial function; (2) Polymersomes and the remaining penicillin can be further released for long-term antibacterial effect. Overall, this polymersome-hydrogel composite demonstrated a new type of injectable antibacterial biomaterial for quick and long-acting antibacterial applications.
Chapter
Malaria remains one of the prime concerns due to its severity. The majority of occurrences of malaria and its resulting deaths are mostly due to infection with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae species. Even though there are about 100 species of Plasmodium that have been identified, these four species are reported to infect humans. Treating malaria at the early stages with antimalarial drugs is the only intervention to save lives. However, due to the development of drug resistance, it becomes an important challenge for malaria control, posing a greater threat for the effective intervention of this disease. Antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine, and artemisinin derivatives have been reported to have developed resistance in major parts of the world. Apart from chemotherapy, developing a vaccine candidate is an effective approach for controlling malarial preventive strategies. The types of malarial vaccines are categorized based on the preerythrocytic, erythrocytic, and transmission blocking stages. With the available vaccine candidates, the efficiency of the several existing vaccines may be implemented through the addition of the adjuvant molecules in which several polymers play a major role in vaccine development. Of those, the paper has reviewed the application of PLGA and PEI materials in malarial vaccine development.
Chapter
Nasal administration is widely used as the logical choice for topical treatment of conditions affecting the nose or paranasal sinuses such as allergic or infectious rhinitis and sinusitis. However, given the rich vascular nature of the nasal mucosa and porous and thin epithelial membrane, the nasal route can also be exploited for systemic drug delivery. It is a promising alternative route for delivering macromolecules, such as peptide and protein drugs and vaccines and is also regarded as a route for delivery of smaller, lower molecular weight drugs that may be subject to first-pass metabolism. In addition, absorption of drug from the olfactory region of the nose provides a potential pathway for drug delivery to the central nervous system (CNS). Nasal administration is less well-suited to the administration of chronic therapies or for those requiring sustained blood levels over time unless they are formulated in a controlled-release system. One strategy to extend delivery times is to decrease the mucociliary clearance (MCC); this can be achieved by increasing the viscosity of the formulation or by enhancing adhesion of the system at the site. This can prolong residence and thus enhance drug absorption. The most common commercially available medicines are solution-based formulations coupled with mucoadhesive systems which may incorporate enzyme inhibitors and nasal permeation enhancers. The first diminishes the enzymatic activity at mucosa, while the latter increases the permeability of the drug, enhances the drug nasal residence time, and improves the therapeutic efficacy of the systemic drugs
Article
Most of the available drugs are usually administered orally (e.g. in tablets or capsules) or by parenteral injection in the case of substances being destroyed in the gastric environment or not being absorbed. However, this bears disadvantages as many people have trouble swallowing tablets and parenteral injection requires trained personnel and/or a reasonably sterile environment to minimize the possibility of contamination. Thus, as an easy to use alternative nasal drug delivery was developed. Drug delivery systems are used to achieve a reproducible high drug concentration. These systems overcome various disadvantages leading to stabilization of the drug, advanced drug transport, improvement of the physicochemical properties of the drug like water solubility, and increase of drug uptake and bioavailability. In addition, properties such as bad taste or smell of the drug are masked. Nasal drug delivery systems are suitable for use both locally and systemically. In the last five years, the development and progression of nasal drug delivery systems has gained importance due to their numerous advantages. This work gives an overview of the basics, such as structure and function of the nose, as well as a short introduction to local and systemic application of drugs. Furthermore, selected drug delivery systems are explained with examples of active ingredients, as well as additional possibilities to increase nasal drug uptake and factors influencing the absorption.
Article
The appropriate delivery of vaccines is a significant factor for the proper immunization. The proper delivery of the cargo vaccine/antigen along with stimulation of high antigen mediated immune response are the prime factors of an efficient vaccine deliver system. Different delivery systems have been explored for vaccine delivery and immunization. However, significant limitations like inefficient immunogenicity and undesired inflammatory immunogenic reactions are also notable. Thus, the development of an efficient vaccine delivery system is challenging task. Polymer based systems have also been utilized for vaccine delivery. Research also have indicated that a polymeric hydrogel can become an efficient delivery system of foreign antigens and vaccines. These systems can harbor and deliver the cargo vaccine/antigen in desired target organ and also facilitate the antigen mediated immunogenicity. Keeping in view the above perspectives, an attempt has been made to review the significance of polymeric hydrogel based systems for vaccine delivery.
Article
The aim of the present research was to investigate the feasibility of developing polylactide-polycaprolactone-polyethylene glycol- polycaprolactone-polylactide (PLA-PCL-PEG-PCL-PLA) based micelles to improve ocular permeability of dexamethasone (DEX). PLA-PCL-PEG-PCL-PLA copolymers were synthesized by a ring-opening polymerization method. DEX was loaded into the developed copolymers. The DEX-loaded micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS) methods. Cytotoxicity of the micelles obtained was investigated on L929 cell line. Cellular uptake was followed by fluorescence microscopy and flow cytometry analyses. The release behavior of DEX from the micelles as well as the drug release kinetics was studied. Corneal permeability was also evaluated using an ex vivo bovine model. The pentablock copolymers were successfully synthesized. The TEM results verified the formation of spherical micelles, the sizes of which was approximately 65 nm. The micelles exhibited suitable compatibility on L929 cells. The release profile showed an initial burst release phase followed by a sustained release phase, the kinetic of which was close to the Weibull's distribution model. The micelles showed higher corneal permeability in comparison to a marketed DEX eye drop. Taken together, the results indicated that the PLA-PCL-PEG-PCL-PLA micelles could be appropriate candidates for the ocular delivery of DEX, and probably other hydrophobic drugs.
Article
Background MAGE family genes have been studied as targets for tumor immunotherapy for a long time. Here, we combined MAGE1-, MAGE3- and MAGEn-derived peptides as a cancer vaccine and tested whether a new combination nanoemulsion-encapsulated vaccine could be used to inhibit the growth of tumor cells in humanized SCID mice. Methods The nanoemulsion-encapsulated complex protein vaccine (MAGE1, MAGE3, and MAGEn/HSP70 fusion protein; M1M3MnH) was prepared using a magnetic ultrasonic technique. After screening, human PBMCs were injected into SCID mice to mimic the human immune system. Then, the humanized SCID mice were challenged with M3-HHCC cells and immunized with nanoemulsion-encapsulated MAGE1-MAGE3-MAGEn/HSP70 [NE(M1M3MnH)] or M1M3MnH. The cellular immune responses were detected by IFN-γ ELISPOT and cytotoxicity assays. Therapeutic and tumor challenge experiments were also performed. Results The results showed that the immune responses elicited by NE(M1M3MnH) were apparently stronger than those elicited by M1M3MnH, NE(-) or PBS, suggesting that this novel nanoemulsion carrier induces potent antitumor immunity against the encapsulated antigens. The results of the therapeutic and tumor challenge experiments also indicated that the new vaccine had a definite effect on SCID mice bearing human hepatic cancer. Conclusion Our study indicated that the combination of several tumor antigen-derived peptides may be a relatively good strategy for peptide-based cancer immunotherapy. These results suggest that the complex nanoemulsion vaccine could have broader applications for both therapy and prevention mediated by antitumor effects in the future.
Article
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Chapter
Much recent progress has been achieved in delivering medications to our bodies. Drug delivery system development has grown exponentially. Some medications have a hurdle of low bioavailability; to counter this, hydrogels have been used as a tool to delimit low bioavailability and side effects. Nanoparticle (NP) and hydrogel composite (NPH) nanoformulations play a significant role in the site-specific or targeted and regulated supply of medicinal products. The field of nanotechnology comprises intracells and particles of 100 nm in size along with devices. Nanoformulations can cross the bloodebrain barrier, improving safety, effectiveness, and patient conformity. These formulations have the following properties: drug loading capability, drug stability, drug release rates, and targeting capacity. Hydrogels are made of cross-connected polymers that can swell out when in contact with water or aqueous media.
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The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.
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The aim of the present study was to investigate the propensity of thiolated chitosan nanoparticles (TCNs) to enhance the nasal delivery of selegiline hydrochloride. TCNs were synthesized by the ionic gelation method. The particle size distribution (PDI), entrapment efficiency (EE), and zeta potential of modified chitosan (CS) nanoparticles were found to be 215 ± 34.71 nm, 70 ± 2.71%, and + 17.06 mV, respectively. The forced swim and the tail suspension tests were used to evaluate the anti-depressant activity, in which elevated immobility time was found to reduce on treatment. TCNs seem to be promising candidates for nose-to-brain delivery in the evaluation of antidepressant activity.
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We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans.Mucosal Immunology advance online publication, 11 February 2015; doi:10.1038/mi.2015.5.
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Book
This book gives a comprehensive overview to all aspects of global molecular vaccine research. It introduces concepts of vaccine immunology and molecular vaccine development for viral, bacterial, parasitic and fungal infections. Furthermore, the broad field of research and development in molecular cancer vaccines is discussed in detail. This book is a must have for scientists and clinicians interested in new developments in molecular vaccine research and application in infections and cancer.