Formulation and Evaluation of Mucoadhesive Microspheres of Pioglitazone Hydrochloride Prepared by Ionotropic External Gelation Technique

Microspheres containing Pioglitazone hydrochloride were prepared by the ionotropic external gelation method, using sodium alginate with four mucoadhesive polymers namely sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose, carbopol 934 P and cellulose acetate phthalate as coat materials. Ionotropic gelation is a method to prepare microspheres using combination of Ca2+ as cationic components and alginate as anion. The practical yield of prepared microspheres using the ionotropic gelation technique was between 172 mg and 604 mg. The result of the Chi-squared test carried out between the actual (practical) and expected (theoretical) yields showed no significant difference (P < 0.05) which indicated that the ionotropic gelation technique could be successfully employed to prepare pioglitazone microspheres using sodium alginate, sodium carboxy methyl cellulose, carbopol 934 P, HPMC, cellulose acetate butyrate polymers. The drug entrapment efficiency of prepared microspheres showed between 56.12% ± 3.86% to 84.68% ± 2.93% which was significantly higher for ionotropic gelation technique. The highest drug entrapment was found in formulation PMI 8. Swelling index is the capability of a polymer to swell before the drug is released which influences the rate and mechanism of drug release from the polymer matrix. The swelling index of prepared microspheres was in the range of 68% ± 4.52% to 87% ± 0.98%. Pioglitazone HCl microspheres showed controlled release of drug without initial peak level achieving. This type of properties in Pioglitazone HCl microspheres used to decrease side effects, reduce dosing frequency and improve patient compliances. From the all batches PMI 8 is considered the best formulation, because among all other formulations, it shows better extent of drug release up to 82.12% (18 h), good entrapment efficiency (84.68%) and the ex-vivo wash-off test shows the best mucoadhesive property. The in vitro drug release studies do up to 18 h. As observed from the various plots, most of the formulations followed the Korsmeyer-Peppas model.

Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles

The aims of this study were to prepare and characterize hydroxypropyl methylcellulose(HPMC)/polycarbophil(PC) mucoadhesive blend films saturated with propranolol hydrochloride(PNL)-loaded nanoparticles to improve permeability of drugs that undergo firstpass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL(70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles(PN-films) and HPMC/PC blend films containing PNL(80 mg/film) without nanoparticles(PPfilms) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope(SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film(PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index(SI)of all PN-films and PP-films increased greatly in the first period time(10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points(10–30 min). After 120 min, the release of PN-films-70 was lower than the other PNfilms. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.

Formulation of a new phenytoin-containing mucoadhesive and evaluation of its healing effects on oral biopsy ulcers

Background and Objective: Several studies have shown the wound healing effect of topical phenytoin, which is applied by its effect on connective tissue intracellular matrix. However, there are still some controversies about its effect on various kinds of wounds, especially in the experimental models. This study is aimed at evaluating the effect of mucoadhesive paste compared to phenytoin mucoadhesive paste on wound healing after oral biopsy. Material and Methods: In this double blind randomized clinical trial, 20 patients who were eligible for oral biopsy were allocated into the case and control groups. After the biopsy, patients having ulcers ranging between one and two centimeters were treated by simple or 1% phenytoin mucoadhesive paste. All patients were instructed to apply their paste at least three times a day for five days after the biopsy. Patients in both groups were evaluated every other day for size of the ulcer, degree of pain and diameter of the inflammatory halo. Statistical analysis was done using SPSS software and Mann-Whitney test. Results: After the second and third appointments, it was observed that the rate of wound healing and decrease in the size of the ulcers were significantly quicker in the treatment group (p = 0.001 and p = 0.003 respectively) and the patients in the phenytoin group reported less pain. Diameter of the inflammatory halo was not significantly different between two groups. Conclusion: Applying 1% phenytoin mucoadhesive paste on biopsy ulcers resulted in accelerated wound healing and decrease in pain, but had no effect on the diameter of the inflammatory halo.

Preparation and evaluation of mucoadhesive bio-flexy films from Cocos nucifera biopolymer using Tiagabine moiety

This research work deals with formulation and evaluation of nanosized Tiagabine loaded bio-flexy films consisting of Cocos nucifera biopolymer(isolated from coconut kernels).Prepared formulations were administered through soft palatal route for brain targeting for epilepsy treatment.Soft palate,part of oral mucosa serves as novel drug delivery platform and mucoadhesive site for systemic drug delivery.It provides sustained and controlled drug delivery system,does not interfere with patient’s regular activities like talking,eating,drinking,etc.It bypasses first-pass metabolism in the liver,reduces dose frequency and minimizes drug’s side effects.Tiagabine,anticonvulsant drug possesses t1/2:7-9 h(low);Protein binding:96%;Water solubility:22 mg/L,acts as selective gamma amino butyric acid(GABA)reuptake inhibitor.Cocos nucifera biopolymer used as bio-excipient to prepare bio-flexy films due to its biodegradability,biocompatibility,non-toxicity,non-irritantancy on soft palatal surface along with inbuilt filmability,mucoadhesive properties.Nanosized drug loaded bio-flexy films were formulated using standard solvent casting method.Bio-flexy films were prepared using varying ratios of nanosized Tiagabine:isolated Cocos nucifera biopolymer(FCT1-FCT6).These prepared formulations were compared with same ratios of nanosized Tiagabine:sodium carboxyl methyl cellulose standard polymer flexy films(FET1-FET6).The%yield of Cocos nucifera biopolymer was found to be 10.2±0.04%.Thickness of nanosized Tiagabine loaded bio-flexy films containing Cocos nucifera biopolymer(FCT1-FCT6)was ranging from 0.026±0.04 mm to 0.040±0.02 mm;Folding endurance:84-107;Surface pH:7.01±0.04 to 7.01±0.02;Weight uniformity:0.012±0.04 to 0.020±0.02;Drug content uniformity:69.5±0.35%to 72.9±0.26%;Swelling percentage:65±0.5%to 73±0.2%;Percentage moisture uptake(PTU):2.0±0.14%to 2.8±0.12%;Mucoadhesivity:20-90 min;Mucoretentivity:60-180 min.The drug release pattern for formulations FCT1-FCT6 containing Cocos nucifera biopolymer based on the T50%and T80%was found to be FCT1(1:0.5)>FCT5(1:6)>FCT3(1:3)>FCT2(1:1)>FCT4(1:5)>FCT6(1:10).Based on all above-mentioned evaluation parameters,FCT1(containing Tiagabine:Cocos nucifera biopolymer(1:0.5))bio-flexy film having R2=0.9221,Higuchi matrix as best fit model,follows anomalous transport release mechanism,T50%:38.45 h.,T80%:41.20 h.using BITS Software 1.12.Stability study revealed stable formulations.Prepared formulations were suitable for soft palatal delivery.

Pre-formulation Study for Preparation of Mucoadhesive Buccal Tablets Containing Nystatin and Cashew Gum by Direct Compression

Cashew gum is a branched chain heteropolysaccharide extracted from the cashew tree (Anacardium occidentale L.).Purified cashew gum (PCG) is free of plant contaminants and is highly soluble.Several studies have indicated this polymer can be relevant in the pharmaceutical industry for production of tablets.Recently,our research group reported that PCG can be used as a diluent for tablets produced by direct compression.Nystatin (Nys) is the drug of first choice for treatment of oral candidiasis,in the form of a suspension.The treatment consists of up to six daily doses of a suspension of nys at 500,000 IU,causing low therapeutic adhesion by patients.The objective of this study was to investigate the behavior of PCG together with nys and other excipients (flavoring agents and lubricating agent) for future manufacture of mucoadhesive buccal tablets by direct compression.For that purpose,we performed pre-formulation tests (FTIR,TGA,XRD,solubility,pH,granulometry,swelling degree and powder flow) with physical mixtures of the drug and excipients.The results were excellent,demonstrating that PCG is a polymer with potential for this type of application.

Topical delivery of acetazolamide by encapsulating in mucoadhesive nanoparticles

The intent of this study was to provide topical delivery of acetazolamide by preparing chitosan-STPP (sodium tripolyphosphate) nanoparticles of acetazolamide and evaluate the particle size, zeta potential, drug entrapment, particle morphology;in vitro drug release and in vivo efficacy. The particles showed sustained in vitro drug release which followed the Higuchi kinetic model. The results indicate that the nanoparticles released the drug by a combination of dissolution and diffusion. The optimised formulation was having particle size 188.46 ± 8.53 nm and zeta potential + 36.86 ± 0.70 mV. The particles were spherical with a polydispersity index of 0.22 ± 0.00. Powder X-ray diffraction and differential scanning calorimetry indicated diminished crystallinity of drug in the nanoparticle formulation. In the in vitro permeation study, the nanoparticle formulation showed elevated permeation as compared to that of drug solution with negative signs of corneal damage. In vitro mucoadhesion studies showed 90.34 ± 1.12% mucoadhesion. The in vivo studies involving ocular hypotensive activity in rabbits revealed significantly higher hypotensive activity (P < 0.05) as compared with plain drug solution with no signs of ocular irritation. The stability studies revealed that formulation was quite stable.

A clinical perspective on mucoadhesive buccal drug delivery systems

Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhe- sire buccal drug delivery systems （MBDDS）, with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems.

Mucoadhesive and antifouling Janus polysaccharide film for prevention of colorectal cancer recurrence post-surgery

Colorectal cancer is one of the most common cancers,and current treatment options include surgery,chemotherapy,and radiation therapy.Most patients undergo surgery,which often requires extensive resection of the colon to prevent recurrence and metastasis of residual malignant tumor cells,leading to postoperative pain and discomfort in daily routines.Although versatile therapeutic patches have been developed to induce tumor apoptosis,achieving both great adhesiveness on the mucus layers of the colon tissue and anti-cell/tissue adhesion to other surrounding organs remains a challenge.Herein,we report a Janus polysaccharide film comprising two polymers:mussel-inspired catechol-conjugated chitosan(Chi-C)with muco-adhesiveness,and alginate(Alg)with anti-adhesion property.The Chi-C and Alg polymers form a stably entangled bilayer film via electrostatic interactions.The Janus film shows a strong tissue adhesive strength of~10 kPa for the Chi-C layer and weak strength of~1 kPa for the Alg layer.Particularly,the Janus film encapsulating an anti-cancer drug exhibits a directional release profile to the tumor site,which is effective for triggering tumor death in in vivo colorectal tumor resection model.Ultimately,such anti-cancer material strategies using bilayered structures are promising for advanced tumor therapy.

Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties:preparation, characterization and application in a vaginal drug delivery system

Lack of mucoadhesive properties is the major drawback to poloxamer 407(F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an aminofunctionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407(F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol(AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels(NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin wasrevealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.

Mucoadhesive microparticles as potential carriers in inhalation delivery of doxycycline hyclate:a comparative study

The present work compares and evaluates the suitability of different polymer-based microparticles for inhalation delivery of doxycycline hyclate.Mucoadhesive polymers,such as sodium carboxymethyl cellulose,sodium alginate,polyvinyl alcohol,polyvinylpyrolidone,starch,and carbopol were selected as carriers for inhalation delivery.Microparticles were prepared by spray drying and evaluated in terms of yield,moisture content,morphology,tapped density,encapsulation efficiency,in vitro mucoadhesion,thermal properties and in vitro aerosolization performance.Additionally,the cytotoxicity of the microparticles on H1299 human alveolar cell line was examined.Smooth spherical to collapsed doughnut shaped particles were formed.They exhibited tap densities of 0.202-0.502 g/cm^(3) and mass median aerodynamic diameter of 3.746.54 um.Mucoadhesion was highest in case of carbopol-based microparticles.Drug release from these microparticles exhibited biphasic Fickian type of diffusion.Only at the highest concentration of microparticles(1 mg/mL)less than 90% cell viability was seen in DX loaded sodium alginate microparticles(DXSA,87.2%),starch microparticles(DXST,85.1%)and carbopol microparticles(DXCP,82.7%)preparations after 48 h of exposure to alveolar cells.The results clearly indicate that sodium carboxymethyl cellulose-based microparticles may serve as an ideal carrier for inhalation delivery of doxycycline hyclate.

Oral colon-targeted mucoadhesive micelles with enzyme-responsive controlled release of curcumin for ulcerative colitis therapy

Although multitudinous nanoscale drug-delivery systems(DDSs)have been recommended to improve anti-ulcerative colitis(UC)outcomes,to enhance the mucoadhesion of nanosystems on the colon and specifically release the loaded drugs in response to the colon micro-environment would be critical factors.The application of curcumin(Cur),an acknowledged anti-UC phytochemical compound,for UC therapy requires more efficient nano-carriers to improve its therapeutic outcome.Herein,we developed the colon-targeted nano-micelles with mucoadhesive effect and Azo reductase-triggered drug release profiles for Cur delivery in UC treatment.Specifically,the amphiphilic block polymer containing the Azo-reductase sensitive linkage(PEG-Azo-PLGA),and catechol-modified TPGS(Cat-TPGS)were synthesized respectively.Based on the self-assembly of the mixed polymers,Cur-micelles(142.7±1.7 nm of average size,72.36%±1.54%of DEE)were obtained.Interestingly,the Cur-micelles exhibited the Azo-reductase sensitive particle dissociation and drug release,the enhanced cellular uptake and the prolonged retention on colonic mucosa,mediated by the strong mucoadhesion of catechol structure.Ultimately,Cur-micelles significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the intestinal flora and the levels of pro-inflammatory factors(MPO,IL-6,IL-1β,and TNF-α)related to TLR4/MyD88/NF-κB signaling pathway.This work provides an effective drug delivery strategy for anti-UC drugs by oral administration.

Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentally- induced dry eye syndrome

Topical formulations, commonly applied for treatment of anterior eye diseases, require frequent administration due to rapid clearance from the ocular surface, typically through the lacrimal drainage system or through over-spillage onto the lids. We report on a mucoadhesive nanoparticle drug delivery system that may be used to prolong the precorneal residence time of encapsulated drugs. The nanoparticles were formed from self-assembly of block copolymers composed of poly（D, L-lactide） and Dextran. The enhanced mucoadhesion properties were achieved by surface functionalizing the nanoparticles with phenylboronic acid. The nanoparticles encapsulated up to 12 wt.% of Cyclosporine A （CycA） and sustained the release for up to five days at a clinically relevant dose, which led us to explore the therapeutic efficacy of the formulation with reduced administration frequency. By administering CycA-loaded nanoparticles to dry eye-induced mice once a week, inflammatory infiltrates were eliminated and the ocular surface completely recovered. The same once a week dosage of the nanoparticles also showed no signs of physical irritation or inflammatory responses in acute （1 week） and chronic （12 weeks） studies in healthy rabbit eyes. These findings indicate that the nanoparticles may significantly reduce the frequency of administration for effective treatment of anterior eye diseases without causing ocular irritation.

Preparation and Characterization of Novel Drug-Inserted-Montmorillonite Chitosan Carriers for Ocular Drug Delivery

The objective of the study was to investigate the potential of montmorillonite as a sustained carrier in the preparation of drug-loaded nanoparticles for prolonged ocular application. Nanoparticles were prepared by ionic gelation of chitosan with sodium tripolyphosphate (TPP). Betaxolol hydrochloride (BH) was applied as a model drug. TG, FT-IR, TEM, DLS and XRD have been employed in the characterization of drug-encapsulated chitosan-montmorillonite/TPP nanoparticles (CS-MMT/TPP NPs). TEM images showed that the particles were spherical in shape and had a rough surface. The size range of the nanoparticles was between 338 and 585 nm with positive zeta potential values from 24 mV to 36 mV and encapsulation efficiency values ranging from 12.27% to 50.92%. In vitro sustained drug release was observed with the BH-loaded nanoparticles in artificial tears (pH 7.4). The results of FT-IR, TG and XRD showed that the drug was coated with CSMMT/ TPP NPs. In the mucoadhesion studies, an interaction was found between drug-loaded CSMMT/ TPP NPs and mucin, which could enhance precorneal residence time and hence facilitate an effective sustained release. The optimized formulation was determined to be non-irritant and tolerable by modified Draize test. Therefore, the BH-loading CS-MMT/TPP NPs developed are a promising carrier for controlled drug delivery to the eye.

Optimization of indomethacin loaded nanostructured lipid carriers

Topical administration is the most common and acceptable use for the treatment of ocular disease.However,the major problem of ocular drug delivery is the rapid drug elimination from the pre-ocular area leading to poor ocular bioavailability[1].Nanostructure lipid carriers(NLC)possess a significant enhancement in ocular bioavailability by increasing the permeability and mucoadhesive property[2].In this study,indomethacin(IND),non-steroidal anti-inflammatory,was used as a model drug[3].

Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

Objective:To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches.Methods:Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose,polyvinyl alcohol,polyvinyl pyrrolidone and ethyl cellulose by solvent casting method.Water impermeable backing layer(Pidilite?Biaxially-oriented polypropylene film)of patches provided unidirectional drug release.They were evaluated for thickness,mass uniformity,surface pH and folding endurance.Six formulations FA2,FA8,FA10,FBI,FB14 and FB16(folding endurance above 250)were evaluated further for swelling studies,ex vivo mucoadhesive strength,ex vivo mucoadhesion time,in vitro drug release,ex vivo permeation,accelerated stability studies and FTIR and XRD spectral studies.Results:The ex vivo mucoadhesion time of patches ranged between 109 min(FA10)to 126 min(FB14).The ex vivo mucoadhesive force was in the range of 0.278 lo 0.479 kg/m/s.The in vitro drug release studies revealed that formulation FA8 released 84%and FB16 released 99.01%of drug in140 min.Conclusions:The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic denvery of carbamazepine.

Exploring the potential of functional polymer-lipid hybrid nanoparticles for enhanced oral delivery of paclitaxel

Most biopharmaceutics classification system(BCS)class IV drugs,with poor solubility and inferior permeability,are also substrates of P-glycoprotein(P-gp)and cytochrome P450(CYP450),leading to their low oral bioavailability.The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles(PLHNs)to enhance the oral absorption of BCS IV drugs.In this paper,taking paclitaxel(PTX)as a drug model,PTX-loaded PLHNs were prepared by a self-assembly method.Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability.Three P-gp inhibitors(D-α-tocopherol polyethylene glycol 1000 succinate,pluronic P123 and Solutol RHS15)were incorporated into selected PLHNs,and a CYP450 inhibitor(the extract of VBRB,BC0)was utilized to jointly promote the drug absorption.Properties of all the PLHNs were characterized systemically,including particle size,zeta potential,encapsulation efficiency,morphology,stability,in vitro drug release,mucoadhesion,in situ intestinal permeability and in vivo systemic exposure.It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested,with absolute bioavailability 21.95%.P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%,8-fold increase compared with that of PTX itself(4.75%).Taken together,our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption,especially for BCS IV drugs.

Surface Topological Glycosylation-Mediated Mucoadhesion of Bacteria

Sugar moieties present on bacterial surface serve as pivotal regulators of bacterial activity.Precisely adjusting the abundance and distribution of surface sugar moieties can offer an important approach to manipulating bacterial behavior,but has been proven to be difficult.Herein,surface topological glycosylation is reported to mediate the interaction of bacteria with mucous layer.Alkynes functionalized by sugar moieties with different branching are synthesized through iterative Michael addition and amide condensation reactions.By a copper-catalyzed azide-alkyne cycloaddition,the resulting compounds with different branching structures can be attached onto bacterial surface that is modified with azido groups.As a proof-of-concept study,a set of topologically glycosylated probiotics(TGPs)is prepared using linear,two-branched,and tetra-branched compounds,respectively.The interaction between mucin and TGPs was studied and the results demonstrate that,compared to unmodified bacteria,TGPs exhibit an enhanced adhesive capacity to mucin,which increases with the branching numbers.Similar binding trend is observed in ex vivo colonic mucus adhesion experiments and bacteria glycosylated with tetra-branched compounds display the highest binding efficiency.This work proposes a chemical method to tune the abundance and distribution of sugar moieties on bacteria,providing unique significant insights into the manipulation of bacterial behavior through surface modification.

Double-layer probiotic encapsulation for enhanced bacteriotherapy against inflammatory bowel disease

Inflammatory bowel disease(IBD)is inflammatory intestinal disorders associated with dysregulated gut microbiota.Bacteriotherapy that leverages bacteria as therapeutics has shown tremendous promise in resolving gut dysbiosis and reducing inflammatory mediators to treat IBD.Orally delivered probiotics,such as Escherichia coli Nissle 1917(EcN),can produce beneficial ingredients,competitively inhibit the proliferation of pathogens,and promote the restoration of gut microbiome homeostasis.However,environmental stresses(such as gastric acids)in the gastrointestinal(GI)tract pose an enormous challenge to the probiotics following oral administration,leading to decreases in viability and activity of probiotics.Meanwhile,the inferior mucoadhesive capability of probiotics results in low colonization efficacy,further compromising their therapeutic effect.Coating probiotics with functional biomaterials may protect them from elimination and prolong their retention in the GI tract.Here,we developed a facile double-layer electrostatic assembly technique to encapsulate EcN bacteria in protective layers of mucoadhesive chitosan(CS)and immunomodulatory hyaluronic acid(HA)to generate HA-CS-EcN.These biomaterials confer the coated EcN resistance to environmental assault and enhanced mucoadhesion in the GI tract.The probiotics equipped with the multifunctional shield can thus suppress inflammation and reshape the intestinal microenvironment to enhance therapeutic efficacy for the prevention and treatment of IBD.Collectively,this study presents a novel probiotic coating strategy to augment the outcome of bacteriotherapy to combat IBD.

Stable oral lubrication enhancer obtained from thiolated polyethylene glycol and mucin

Mucins are vital components contributing to the unique lubrication properties of human whole saliva.For patients receiving medication and or treatment such as diabetes or radiotherapy,xerostomia(dry mouth)is a common with numerous and deleterious side effects.Although products exist on the market to relive the symptoms of Xerostomia there remains a drive to formulate a biocompatible lubricant that replicate the functionality offered by the natural biological environment.Herein,a combination of mucin and thiolated polyethylene glycol(PEG-SH)was proposed as a new saliva substitute.Mucin and PEG-SH molecules could form hydrated layers immediately by chemisorption.Meanwhile,the chemical interactions between mucin and PEG-SH molecules also promoted the formation of a mixed layer.All the pre-formed layers could decrease friction and had the potential to decrease wear,especially mucin and PEG-SH mixed layer when compared to mucin only solutions.Further investigations of tribological mechanism implied that the excellent lubrication performance of mixed layer with long effectiveness was contributed to the frictionreducing effect of PEG/mucin molecules and the mucoadhesive property of mucin.The study provides a guide for using mucin as a mucoadhesive agent to stable lubricative polymers with low molecular weight as novel salivary substitutes for lubrication.

Recent advances in alginate based gastroretentive technologies for drug delivery applications

The efficacy of orally delivered medicines can be maximized through enhancing the gastric residence period and modifying the drug release pattern according to therapeutic need.Several technologies were investigated through recent years for increasing gastric retention of medicines.Biopolymers are one of the widely studied materials for increasing the retention of drug delivery systems in the stomach region.The biodegradability,biocompatibility and non-toxic behavior in combination with the easy fabrication technologies has made biopolymers an interesting option to pharmaceutical scientists for developing gastroretentive drug delivery systems(GRDDS).Several gastroretentive approaches are reported to be efficacious to localize the drug delivery system in the gastric region.Alginates are commonly employed polysaccharide for developing various GRDDS including low density systems,mucoadhesive systems,swellable systems,hydrogel forming systems,in situ gelling systems,raft forming systems,magnetic systems.The abundant availability from marine and bacterial sources in combination with its attractive physicochemical nature has encouraged pharmaceutical researchers to investigate its suitability in developing various drug delivery system.The mucoadhesive,hydrogel forming and raft forming behavior of alginates makes alginate suitable for GRDDS.The attractive properties of alginate makes it a useful biopolymer in the biomedical field.This review focuses on the source and chemistry of alginates and describes the applications of alginates in developing novel gastroretentive drug delivery systems.