Mucoadhesive Nature Research Articles

A review on exploring the potential of PVA and chitosan in biomedical applications: A focus on tissue engineering, drug delivery and biomedical sensors.

Polymers have been integral to the advancement of biomedicine, owing to their exceptional versatility and functionality. Among these, polyvinyl alcohol (PVA) and chitosan both natural polymers stand out for their remarkable biocompatibility, biodegradability, and unique properties. This review article provides a comprehensive examination of the diverse applications of PVA and chitosan in three pivotal areas: tissue engineering, drug delivery, and biosensors. In tissue engineering, the discussion centres on how PVA and chitosan are engineered into scaffolds that not only support cell growth and differentiation but also promote tissue regeneration by closely mimicking the extracellular matrix. These scaffolds offer the necessary mechanical strength and adaptability for various biomedical applications. For drug delivery, the article delves into the development of sophisticated controlled release systems and targeted drug carriers, highlighting the polymers' customizable properties and their mucoadhesive nature, which make them highly effective across multiple drug delivery methods. Furthermore, the potential of PVA and chitosan in biosensor technology is explored, particularly their ability to interact with biomolecules and their intrinsic conductivity attributes that are essential for creating sensitive, reliable, and biocompatible sensors for medical diagnostics. By synthesizing recent research findings and suggesting future research directions, this review underscores the versatility and critical role of PVA and chitosan in pushing the boundaries of biomedical innovation. It offers valuable insights for researchers and scientists dedicated to advancing healthcare through the application of these natural polymers.

Potentiation of Brain Bioavailability Using Thermoreversible Cubosomal Formulation.

The aim of the present study was to develop and evaluate intranasal formulations of the thermoreversible fluoxetine cubosomal in situ gel. This gel was intended for permeation and bioavailability enhancement to target the brain effectively by bypassing the blood-brain barrier (BBB). Fluoxetine-loaded cubosomes were prepared by the homogenization method followed by the cold method approach to develop in situ gel. Fluoxetine-loaded cubosomes displayed a higher encapsulation efficiency (82.60 ± 1.25%) than fluoxetine. This might be due to the solubilizing activity of the polymer to cause partitioning of the lipophilic drug into the aqueous phase during the change from the cubic gel phase to cubosomes. In vitro analysis of fluoxetine-loaded cubosomal in situ gel showed a sustained release profile (93.22 ± 2.47%) due to limited diffusion of fluoxetine. The formation of strong affinity bonds of the drug with GMO (drug transporter) decreased the drug release in comparison to that with fluoxetine-loaded cubosomes (90.68 ± 1.74%). The ex vivo drug release profile revealed the drug release of 96.31 ± 2.88% by the end of 24 h. This is attributed to the higher capability of the intranasal cubosomal in situ gel to prolong the retention and enable better permeation through the nasal mucosa. In male Wistar rats, in vivo biodistribution studies for cubosomal in situ gel administered via the intranasal route at a dose of 3.5 mg/kg demonstrated an increase in pharmacokinetic parameters like the AUC (406 ± 75.35 μg/mL), Cmax (368.07 ± 0.23 μg/mL), Tmax (4 h), and t1/2 (14.06 h). The mucoadhesive nature of the in situ gel led to an increase in the residence time of the gel in the nasal mucosa. The biodistribution study of intranasal in situ cubosomal gel improved the bioavailability 2.21-fold in comparison to that with the cubosomal dispersion but 2.83-fold in comparison to that with the drug solution. Therefore, fluoxetine-loaded cubosomal in situ gel proved as a promising carrier for effective transportation of fluoxetine via the intranasal route with significant brain bioavailability.

A Review on Natural Polymer Tamarind Seed Polysaccharide

The developing interest in normal polymers for different applications has brought tTamarind seed polysaccharide (TSP) into the spotlight. Gotten from Tamarindus indica seeds, TSP’s special properties make it a convincing biopolymer. This complete audit investigates TSP’s attributes, extraction techniques, and far reaching applications. Featuring its part in drug delivery, wound healing, and then some, the audit highlights TSP’s biocompatibility, mucoadhesive nature, and adaptability. While TSP offers various advantages, challenges like extraction hardships and variable organization exist. Future possibilities in drugs include progressed drug delivery system, biocompatible supplements, and creative oral definitions. The survey likewise underscores the requirement for thorough clinical preliminaries, protected innovation contemplations, and joint effort for TSP’s fruitful interpretation into certifiable applications. In general, TSP emerges as a promising biopolymer with significant industry-wide potential

Designing aloe vera-sterculia gum based copolymeric hydrogel dressings for drug delivery

Herein the present work, aloe vera (AV) and sterculia gum (SG) based polymer network hydrogels have been designed for use in wound dressing and drug delivery (DD) applications. The hydrogels were prepared by graft copolymerization reaction of poly(2-(methacryloyloxy) ethyl trimethylammonium chloride) [poly (METAC)] onto AV and SG. Polymers were characterized by FESEM, SEM, EDS, AFM, C13 NMR, FTIR, XRD and TGA-DTG analysis. Swelling, drug delivery and biomedical properties of dressings have been evaluated. Sustained diffusion of moxifloxacin drug from dressings exhibited a non-Fickian diffusion mechanism and the release profile was best fitted in the Korsmeyer-Peppas kinetic model. Various interactions of polymers with blood and goat membranes revealed the biocompatible and mucoadhesive nature of the dressings. Hydrogel dressings were found permeable to O2 and water vapour and impermeable to microbes. Overall, these properties revealed that these hydrogels could act as suitable materials for design of wound dressings. Furthermore, antioxidant properties of AV, wound healing characteristic of SG, antibacterial properties of poly(METAC) and encapsulated moxifloxacin drug in hydrogel dressings may enhance the wound healing potential of hydrogel wound dressings (HWD).

Biophysical analysis on molecular interactions between chitosan-coated sinapic acid loaded liposomes and mucin

BackgroundThe mucus biomembrane is a primary barrier in delivering drugs to the brain via intranasal delivery. The negatively charged nanoformulations suffer from poor mucoadhesive ability and less retention time in the nasal cavity, which limits further therapeutic efficacy. The positively charged chitosan coating on liposomes may overcome the above issues. Hence, understanding the molecular interactions between the chitosan-coated liposomes and mucin is essential for developing an effective drug delivery system. MethodsThe molecular interactions of mucin with sinapic acid-loaded liposomes (SA-LPs) and mucin with chitosan-coated sinapic acid-loaded liposomes (SA-CH-LPs) were assessed using different biophysical instrumental analyses by interpreting the UV–Vis spectra and observing the particle size, polydispersity index, surface charge, and rheological behavior. ResultsThe mucin interaction with SA-CH-LPs showed increased viscosity as compared to SA-LPs with mucin. Moreover, the mucin interaction with SA-CH-LPs showed stronger mucoadhesive properties as compared to SA-LPs with mucin. The electrostatic interaction between positively charged SA-CH-LPs and negatively charged mucin was responsible for the enhanced mucoadhesive property. ConclusionThe positively charged SA-CH-LPs highly interact with mucin as compared to negatively charged SA-LPs. The mucoadhesive property of SA-CH-LPs could improve the retention of SA in the nasal cavity as compared to SA-LPs. These findings emphasize the importance of chitosan in modulating the mucoadhesive behavior of liposomes. General significanceOverall, this study helps to understand the molecular interactions and mucoadhesive nature of the chitosan-coated liposomes with mucin, which is essential for biological activity in the physiological environment.

Exploring neem gum in designing hydrogel dressings by covalent and supra-molecular interactions for better wound healing

Neem gum is a bioactive polysaccharide that has various therapeutic applications. Herein, it was explored in designing network structure in the form of hydrogel wound dressings (WD) by covalent and supramolecular interactions. These hydrogel dressings were encapsulated with the antibiotic drug cefuroxime for better wound healing. SEM and AFM showed surface heterogeneity with a rough surface of the hydrogel network. 13C-NMR and FTIR demonstrated incorporation of carbopol and poly (vinylsulphonic) (VSA) in dressings. XRD and TGA indicated the amorphous state of copolymers with improved thermal properties. Interactions of copolymers with drug, blood, and bio-membrane have revealed sustained drug release, blood-compatible and mucoadhesive nature of hydrogel dressings which have capacity to absorb 8.50 ± 0.18 g/g of simulated fluid. Dressings were O2 and H2O vapour permeable. The diffusion mechanism of the antibiotic drug cefuroxime was found Fickian-type with first- order kinetic model. Antibacterial character of polymeric hydrogels was found against microbes during the antimicrobial test. These properties advocated these hydrogels as materials for WD and drug delivery (DD).

Colon-Adhering Delivery System with Inflammation Responsiveness for Localized Therapy of Experimental Colitis.

Ulcerative colitis (UC) is a chronic inflammation-related disease that severely affects the colon and rectum regions. A variety of therapy regimens are used for the treatment of UC. Clinically, therapeutic enema is the choice of therapy for UC patients. Irrespective of on-site administration, the major limitation of therapeutic enemas is the dispossession of the medicine followed by low drug availability for the therapeutic action. In our present work, we have developed an enzyme-responsive injectable hydrogel (ER-hydrogel) to overcome the limitations of therapeutic enema. The hydrogels possess two major advantages, which are being exploited for therapeutic drug delivery in UC: prolonged retention and enzyme responsiveness. The former is one of the prominent advantages of hydrogel compared to free drug enema and the latter controls the release of the drug or provides drug release on-demand. The ER-hydrogel was formulated by the heat-cool method and for therapeutic purposes, a corticosteroid drug, budesonide (Bud), was encapsulated into the ER-hydrogel and evaluated for its various physicochemical and therapeutic potentials in dextran sodium sulfate (DSS)-induced UC. In vitro and ex vivo adhesion studies confirm the retention or mucoadhesive nature of the ER-hydrogel, and the upsurge in Bud release from the Bud-loaded ER-hydrogel upon the addition of esterase enzyme confirms the enzyme-mediated drug release from the ER-hydrogel. Moreover, Bud-loaded ER-hydrogel exhibited promising results in alleviating the disease activity index of UC, and restored the length of the colon, which is the main hallmark of UC. In terms of the health of the colon tissue, the Bud-loaded ER-hydrogel restored the colonic tissue damage, as seen in the H&E-stained, AB-NR-stained, and HID-AB-stained colon sections. Finally, the Bud-loaded ER-hydrogel also markedly subsided the IL-1β, TNF-α, MPO, and nitrite levels in serum and colon tissues. Thus, the fabricated Bud-loaded ER-hydrogel possesses appreciable translational potential due to its ability to significantly ameliorate inflammatory changes compared to naive or water-based therapeutic enema in acute experimental colitis in mice.

Developing 3D-network gels from polysaccharide gums for biomedical applications

Keeping in view the recent advancements in polysaccharide materials, gum acacia (GA) - tragacanth gum (TG) was investigated for designing polymeric network structures impregnated with cephalexin antibiotics for drug delivery (DD). Grafted product of polyvinylimidazole [poly(VIm)] and GA-TG was characterized by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Change in mesh size (from 17.73 to 32.98 nm) and crosslinking density (between 1.64 × 10−5 to 5.06 × 10−5 mol cm−3) was found with change in poly(VIm), gum and crosslinker NNMBA content which revealed that these parameters can be tailored made as per requirement and applications. Swelling properties illustrated pH sensitivity in copolymers because of composition which is useful for colon or site-specific DD of cephalexin. FESEM and AFM demonstrated heterogeneous morphology with the rough surface topology of grafted product. XPS and FTIR confirmed the grafting of poly(VIm) onto polysaccharide chains. Drug diffusion was non-Fickian and release was fitted in Higuchi kinetic model from copolymers. The release was slow and prolonged due to drug-polymer interactions. Copolymers exhibited 31.29% scavenging ability in DPPH assay and haemolysis was less than 2% that inferred biocompatible nature. Bio-surface interactions with intestinal membrane indicated the muco-adhesive nature of copolymers. Antimicrobial properties of hydrogel were evaluated against E. coli, P. aeruginosa and S. aureus. All observations revealed that GA-TG crosslinked copolymers could be explored for colon DD of antibiotic drugs with tailored crosslinking density.

Reactive oxygen species-responsive thymine-conjugated chitosan: Synthesis and evaluation as cryogel

Chitosan (CS) is a biodegradable, biocompatible cationic polysaccharide based natural polymer with antibacterial and anti-inflammatory properties. Hydrogels made from CS have found their applications in wound healing, tissue regeneration and drug delivery. Although, mucoadhesive properties are resulted from the polycationic nature of CS, in hydrogel form amines are engaged in interactions with water leading to decrease in mucoadhesive properties. In case of injury, presence of elevated level of reactive oxygen species (ROS) has inspired many drug delivery platforms to conjugate ROS responsive linkers for on demand drug delivery. In this report we have conjugated a reactive oxygen species (ROS) responsive thioketal (Tk) linker and nucleobase thymine (Thy) with CS. Cryogel from this doubly functionalized polymer CS-Thy-Tk was prepared through crosslinking with sodium alginate. Inosine was loaded on the scaffold and studied for its release under oxidative condition. We anticipated that the presence of thymine shall retain the mucoadhesive nature of the CS-Thy-Tk polymer in hydrogel form and when placed at the site of injury, due to the presence of excessive ROS at inflammatory condition, loaded drug shall release due to degradation of the linker. Porous cryogel scaffold was prepared via chemical crosslinking of amine functional group of chitosan with carboxylic acid containing polysaccharide sodium alginate. The cryogel was evaluated for porosity (FE-SEM), rheology, swelling, degradation, mucoadhesive properties and biocompatibility. Resulted scaffold was found to be porous with average pore size of 107 ± 23 μm, biocompatible, hemocompatible and possesses improved mucoadhesive property (mucin binding efficiency of 19.54 %) which was found to be 4 times better as compared to chitosan (4.53 %). The cumulative drug release found to be better in the presence of H2O2 (∼90 %) when compared to that of PBS alone (∼60–70 %). Therefore, the modified CS-Thy-TK polymer may hold potential as interesting scaffold in case of conditions associated with elevated ROS level such as injury and tumor.

Fabrication of acacia gum grafted copolymeric network hydrogel for biomedical applications

Keeping in view therapeutic role of gum polysaccharides and to explore advancements in research expectancy in area of gum for future research for development of new materials for biomedical applications, in present research, acacia gum was grafted with poly(acrylamide) [poly(AAm)] and poly(2-arylamido-2-methylpropanesulfonic acid) poly(AMPSA) to design hydrogels by copolymerization for use in drug delivery of levofloxacin antibiotic drug. These co-polymers were characterized by SEMs, AFM, FTIR, 13C NMR, XRD and TGA. The SEM indicated uneven surface due to grafting and AFM confirmed the surface roughness for better mucoadhesion. The prominent peaks at 178.871 ppm and 52.180 ppm indicated the incorporation of the AAM and AMPSA due to CO and C–S into copolymer by grafting reaction. XRD indicated the amorphous region and TGA reflected three stages thermal decomposition. The results reflected slow release of drug due to supra-molecular interactions between drug and copolymers and diffusion of drug occurred with non-Fickian mechanism from network hydrogels with first order kinetic release model. The copolymeric material showed radical scavenging activity was 26.12 ± 2.23% in DPPH assay and 3.42 ± 0.396% hemolytic index values. The network copolymers also showed 0.281 ± 0.093 N peak detachment force from mucoadhesive test. The results of biomedical assay inference the non-hemolytic behavior with antioxidant and mucoadhesive nature of the network copolymers. These results signified the suitability of the polymeric materials for colon specific drug delivery.

Radiolabelled folate micellar carriers as proposed diagnostic aid for CNS tumors by nasal route.

Glioma refers to the most atypical variant of the malignant central nervous system tumors posturing massive challenge to the research fraternity owing to the flimsy improvement in the patient survival rate over the past years. The aim of the proposed work was developing a diagnostic aid for brain tumors, which could be administered via the non-invasive intranasal route. Since overexpression of folate receptors in the central nervous system tumors is 500 times more than the normal healthy cells, we aimed at fabricating a radiolabeled folate encapsulated micellar delivery system to be given via the nasal route. Folate conjugated bifunctional chelating agent was synthesized, radiolabeled with 99mTc, and encapsulated in a micellar carrier. The fabricated micelles were further evaluated for in vivo nasal toxicity in rats and the same were found safe for intranasal administration. The fabricated micelles owing to their nano size, mucoadhesive nature, and enhanced permeation were observed to have a higher uptake into the brain (around 16% in 4 h) than as compared to the radiolabeled conjugated folate solution when studied for in vivo biodistribution in mice. Single-photon emission computerized tomography imaging performed in higher animals upon intranasal administration of the micellar formulation revealed enhanced uptake of the micelles into the animal brain. It is believed that the aforementioned formulation can be of a great diagnostic value in the detection of not only brain tumors but also other folate expressing cancers such as cervical, breast, and lungs as the system is fast, non-toxic, accurate, non-invasive, and simple.

Mucoadhesive Cationic Bromelain Laden Nanocarriers Restore Patency of Airway Hyperresponsive Remodeling via Nasal Route

AbstractBromelain, a complex mixture of proteolytic cysteine proteases has shown positive attributes in management of allergen induced inflammatory conditions. However, efficient use of bromelain in clinics is restricted by bromelain instability at storage conditions and on oral use. Therefore, the goal of present investigation is to encapsulate bromelain in rationally tailored mucoadhesive polymeric nanocarriers for nasal delivery to refurbish its anti‐asthmatic activity and improve bioavailability. Bromelain laden Eudragid RL 100 nanocarriers (Br‐EuNCs) are engineered via double emulsion solvent evaporation method and optimized to amplify bromelain encapsulation within nanosize range (259.73 ± 16.51 nm). Dissolution study reveals prolonged bromelain release behavior (24 h) whereas higher mucin binding strength confirms mucoadhesive nature of Br‐EuNCs. Pharmacokinetic study in rats indicates 2.89‐fold increase in bromelain bioavailability after its encapsulation. Subsequently, pharmacodynamic studies reveal that optimized formulation significantly (p <0.05) reduces spasm, bronchial hyper‐responsiveness and inhibits convulsions in the ovalbumin induced asthma model. In addition, Br‐EuNCs significantly regulate hematological, biochemical, and immunological parameters disturbed during ovalbumin exposure. Histological studies of lung show significant protectionoffered by formulation against tissue damage during asthma. The results suggest that therapeutic performance of bromelain can be improved utilizing Br‐EuNCs as a platform via nasal route for asthma management.

REVIEW ON MUCOADHESIVE DRUG DELIVERY SYSTEMS

This review considers the basic mechanisms by which mucoadhesive can adhere to a mucous membrane in terms of the nature of the adhering surfaces and the forces that may be generated to secure them together.it also include contact stage and consolidation stage. Mucosal adhesion is backed by several theories. Much attention has been focused in the field of mucoadhesive formulation developments compared to other delivery systems. Mucoadhesion while considering drug delivery is having several merits, because of the ideal physiochemical characters of the mucosal membrane. Ideally a mucoadhesive dosage form interacts with the mucosal membrane by ionic bonds, covalent bonds, Van-der-Waal bonds and hydrogen bonds. Various sites for mucoadhesive drug delivery system are ocular, nasal, buccal cavity; GIT, vaginal, rectal and several specific dosage forms have been reported. Factors affecting mucoadhesion are molecular weight, flexibility of polymer chain, pH, presence of carboxylate group and density. Several synthetic and natural polymers are identified as suitable candidates for mucoadhesive formulation. Ex-vivo/in-vitro studies utilizing gut sac of rats provides in-depth knowledge about the adhesive property of the dosage form as well as polymers. AFM can be used as a part of imaging methods. Mucoadhesive drug delivery system shows promising future in enhancing the bioavailability and specific needs by utilizing the physiochemical characters of both the dosage form and the mucosal lining. It has to be noted that only a moist surface can bring the mucoadhesive nature of the dosage form.

Exploration of the high energy radiation for the designing of psyllium-poly(MEDSAH) zwitterionic superabsorbent hydrogels for biomedical uses

The main objective of the present work is to develop the hydrogels as drug delivery carrier for the antibiotic drug ciprofloxacin by using graft copolymerization reaction of poly 2-(Methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide [poly(MEDSAH)] onto a bioactive dietary fiber psyllium. High energy gamma radiations were applied for the formation and sterilization of network hydrogels simultaneously. The release profile of the antibiotic drug ciprofloxacin was determined to evaluate the diffusion mechanism. Biomedical assay of polymers was also evaluated by determining the blood compatibility, antioxidant, mucoadhesive and degradation properties of the psyllium-poly(MEDSAH) network hydrogels prepared for drug delivery (DD) applications. The polymers were characterized by 13C NMR, FTIR, TGA/DTG, DSC, SEM, AFM and XRD. TGA confirmed thermal stability while SEM and AFM indicated porous and rough surface of the polymers. Both, zwitterionic monomer and radiation dose changed mesh size (from 87.94 to 529.33 nm) and crosslinking density (from 0.33 × 10−6 to 12.13 × 10−6 mol/cm3). The grafted polymers showed antioxidant nature of the material which exhibited 48.99 ± 1% free radical scavenging in DPPH assay. Polymer indicated biocompatible nature which showed 81.02 ± 5.91% thromboses percentage and less than 2% hemolytic index during blood-polymer interactions. Furthermore, detachment force required to detach the polymer from mucous membrane was Fmax=0.169 ± 0.035 N which required work of adhesion Wad=0.125 ± 0.014 N.sec showing the mucoadhesive nature of the polymeric hydrogels. The antibiotic drug ciprofloxacin diffusion occurred slowly with non-Fickian mechanism and Korsmeyer-Peppas model. Overall, results reflected their suitability of these DD carriers for colon in slow and sustained manner.

Design of moxifloxacin encapsulated network hydrogel wound dressings: Evaluation of polymer‐drug, polymer‐blood, and polymer‐bio membrane interactions

AbstractIt is an exploration of the inherent wound‐healing tendency of Azadirachta indica gum (AIG) or neem gum polysaccharides to develop the hydrogel wound dressings with enhanced potential during wound management. Herein this research work, antibiotic moxifloxacin encapsulated AIG network copolymeric hydrogels were developed by functionalizing with carbapol and poly(acrylamide) [poly(AAm)] for better wound healing. The polymer‐drug, polymer‐blood, and polymer‐bio membrane interactions were evaluated in biomedical properties. The copolymeric network structure was confirmed by scanning electron micrographs (SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and 13C solid‐state nuclear magnetic resonance (NMR) spectroscopy. The results confirmed sustained release of the moxifloxacin with diffusion by non‐Fickian process and Korsmeyer–Peppas kinetic model in the phosphate buffer saline (PBS). These interactions inferred the blood‐compatible (hemolytic index 3.41 ± 0.70%) and mucoadhesive nature (polymer‐biomembrane detachment force 0.09 ± 0.01 mN) of hydrogel dressing. The per gram of hydrogel dressings absorbed 10.22 ± 0.23 g of simulated wound fluid which is very useful to maintain moist wound environment for better wound healing. All these interactions and properties indicated the suitability of the hydrogel material for wound dressing applications for better wound care.

Tailoring and evaluating poly(vinyl sulfonic acid)-sterculia gum network hydrogel for biomedical applications

In the present work, sterculia gum has been explored to devise the network structure via grafting of poly (vinyl sulfonic acid) (VSA) for biomedical uses. The grafted network hydrogels showed 3.848 ± 1.00% haemolytic potential, 92.00 ± 17.00 mN detachment force with mucosal surface and 13.13 ± 0.49 g/g colonic simulated fluid sorption, respectively. The copolymeric networks were characterized by SEMs, AFM, FTIR, XRD, solid state 13C-NMR, and TGA- DSC. The mesh size was increased from 16.65 nm to 35.67 nm by changing pH from pH 2.2 to pH 7.4 buffer. The hydrogel showed 34.00 ± 4.68% porosity and 38.44 ± 2.88% of antioxidant activity. Non-Fickian diffusion of drug occurred in controlled manner from sterculia-cl-poly(VSA) network hydrogels which was due to supra-molecular interactions of vancomycin drug - sulfonated polymers and release profile was fitted in Higuchi kinetic model. The various interactions indicated the non-hemolytic, mucoadhesive nature of the polymers. These results signified the suitability of the biomedical polymer for colon specific drug delivery applications.

Enhancement of mechanical properties of chitosan film by doping with sage extract-loaded niosomes

Chitosan films are increasingly being applied in the biomedical field owing to their biocompatibility, biodegradability, non-toxicity, mucoadhesive nature, hemostatic properties, antibacterial and biological activities. This study aimed to enhance the mechanical properties of chitosan films by doping niosomal sage nanoparticles (NS-SagNPs) at various concentrations (100–300 μg). The NS-SagNPs were prepared by a thin-film hydration process with an average particle size of 21.5 nm. The doped chitosan films were fabricated through a simple casting method. FTIR and DSC measurements confirmed the successful incorporation of NS-SagNPs in the chitosan films. The mechanical properties of the doped films were improved and the most significant improvement was found in tensile strength and elasticity when the NS-SagNPs loading was increased to 300 μg. Based on these results, chitosan films doped with NS-SagNPs have the advantageous feature of sage and show enhanced mechanical properties compared with pure chitosan, rendering them more suitable for biomedical applications.

Photothermal Activatable Mucoadhesive Fiber Mats for On-Demand Delivery of Insulin via Buccal and Corneal Mucosa.

Electrospun fiber mats loaded with therapeutics have gained considerable attention as a versatile tool in the biomedical field. While these bandages are largely based on fast-dissolving polymers to release the cargo, stimuli-responsive fiber mats have the advantages of providing a timely and spatially controlled drug delivery platform, which can be refilled and reused several times. These benefits make electrospun fiber patches original platforms for painless and convenient on-demand hormone release. Because of the high need of more convenient and non-invasive methods for delivering insulin, a hormone that is currently used to treat hundred million people with diabetes worldwide, we have investigated the tremendous potential of reduced graphene oxide modified poly(acrylic acid) based fiber mats as an original platform for buccal and corneal insulin delivery on-demand. The PAA@rGO hydrogel-like fibers rendered water-insoluble by incorporating β-cyclodextrin, followed by thermal cross-linking, which showed adequate tensile strength along with high adsorption capacity of insulin at pH 7 and good recyclability. The fiber mats maintained good fibrous morphology and high loading efficiency even after five loading-release cycles. The mucoadhesive nature of the fibers allowed their application for insulin delivery via the eye cornea and the buccal mouth lining, as evidenced in ex vivo studies. Insulin loaded PAA@rGO hydrogel-like fibers showed an insulin flux via buccal lining of pigs of 16.6 ± 2.9 μg cm-2 h-1 and 24.3 ± 3.1 μg cm-2 h-1 for porcine cornea. Testing on healthy adult volunteers confirmed the excellent, mucoadhesive nature of the bandage, with three out of six volunteers feeling completely comfortable (note 8.3) while wearing the patches in the buccal cavity.

Lipid Cubic Systems for Sustained and Controlled Delivery of Antihistamine Drugs.

Antihistamines are capable of blocking mediator responses in allergic reactions including allergic rhinitis and dermatological reactions. By incorporating various H1 receptor antagonists into a lipid cubic phase network, these active ingredients can be delivered locally over an extended period of time owing to the mucoadhesive nature of the system. Local delivery can avoid inducing unwanted side effects, often observed after systematic delivery. Lipid-based antihistamine delivery systems are shown here to exhibit prolonged release capabilities. In vitro drug dissolution studies investigated the extent and release rate of two model first-generation and two model second-generation H1 antagonist antihistamine drugs from two monoacyglycerol-derived lipid models. To optimize the formulation approach, the systems were characterized macroscopically and microscopically by small-angle X-ray scattering and polarized light to ascertain the mesophase accessed upon an incorporation of antihistamines of varying solubilities and size. The impact of encapsulating the antihistamine molecules on the degree of mucoadhesivity of the lipid cubic systems was investigated using multiparametric surface plasmon resonance. With the ultimate goal of developing therapies for the treatment of allergic reactions, the ability of the formulations to inhibit mediator release utilizing RBL-2H3 mast cells with the propensity to release histamine upon induction was explored, demonstrating no interference from the lipid excipient on the effectiveness of the antihistamine molecules.

Endogenous Conjugation of Biomimetic Dinitrosyl Iron Complex with Protein Vehicles for Oral Delivery of Nitric Oxide to Brain and Activation of Hippocampal Neurogenesis.

Nitric oxide (NO), a pro-neurogenic and antineuroinflammatory gasotransmitter, features the potential to develop a translational medicine against neuropathological conditions. Despite the extensive efforts made on the controlled delivery of therapeutic NO, however, an orally active NO prodrug for a treatment of chronic neuropathy was not reported yet. Inspired by the natural dinitrosyl iron unit (DNIU) [Fe(NO)2], in this study, a reversible and dynamic interaction between the biomimetic [(NO)2Fe(μ-SCH2CH2OH)2Fe(NO)2] (DNIC-1) and serum albumin (or gastrointestinal mucin) was explored to discover endogenous proteins as a vehicle for an oral delivery of NO to the brain after an oral administration of DNIC-1. On the basis of the in vitro and in vivo study, a rapid binding of DNIC-1 toward gastrointestinal mucin yielding the mucin-bound dinitrosyl iron complex (DNIC) discovers the mucoadhesive nature of DNIC-1. A reversible interconversion between mucin-bound DNIC and DNIC-1 facilitates the mucus-penetrating migration of DNIC-1 shielded in the gastrointestinal tract of the stomach and small intestine. Moreover, the NO-release reactivity of DNIC-1 induces the transient opening of the cellular tight junction and enhances its paracellular permeability across the intestinal epithelial barrier. During circulation in the bloodstream, a stoichiometric binding of DNIC-1 to the serum albumin, as another endogenous protein vehicle, stabilizes the DNIU [Fe(NO)2] for a subsequent transfer into the brain. With aging mice under a Western diet as a disease model for metabolic syndrome and cognitive impairment, an oral administration of DNIC-1 in a daily manner for 16 weeks activates the hippocampal neurogenesis and ameliorates the impaired cognitive ability. Taken together, these findings disclose the synergy between biomimetic DNIC-1 and endogenous protein vehicles for an oral delivery of therapeutic NO to the brain against chronic neuropathy.