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 manipulatin...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.展开更多
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 loa...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.展开更多
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 bioavailab...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.展开更多
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 h...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.展开更多
Oral and maxillofacial diseases are a group of high-incidence disorders that affect people’s life quality to a great extent,while the wet and highly movable environment of the related regions brings challenges to tra...Oral and maxillofacial diseases are a group of high-incidence disorders that affect people’s life quality to a great extent,while the wet and highly movable environment of the related regions brings challenges to traditional therapies.Faced with the obstacles of insufficient adhesive strength and ensuing short drug retention time,conventional oral therapeutic agents often have difficulty in achieving their desired efficacy.Oral and maxillofacial wet-adhesive materials have the advantages of excellent wet environment retention,internal stability,plasticity,and clinical potential,thus have become a significant research direction in the field of oral related disorders healing.In the past decade,the development of oral adhesive materials with good wet adhesion has accelerated based on the chemical molecular interaction,physical interlocking,and biological adhesion mechanisms,including biomimetic-inspired materials,naturally derived polymer–based materials and adhesive electrospun fiber films.These fancy wet-adhesive materials can be used for oral mucosal drug delivery,oral vaccination,wound healing,and bone defects treatments.Despite their numerous novel applications,wet-adhesive materials in stomatology still face unresolved challenges from material and biological aspects.Here,advances in designs of oral and maxillofacial wetadhesive materials are reviewed in terms of design backgrounds,attachment mechanisms,and common classifications.Recent demonstrations of wet-adhesive materials for oral and maxillofacial region medical applications from drug delivery to multifunctional tissue treatments are presented.To conclude,current challenges and prospects on potential applications of oral and maxillofacial wet-adhesive materials are also briefly discussed.展开更多
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 entrap...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.展开更多
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 ro...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.展开更多
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...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 Ca<sup>2+</sup> 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.展开更多
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 io...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.展开更多
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...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].展开更多
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 perm...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.展开更多
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...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.展开更多
The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis.The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so ...The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis.The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment.The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method.Microcry stalline cellulose was used as the filler and its effect was also studied.The prepared dosage forms were evaluated for physicochemical properties,in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue.Tablets containing 50% of polymers(Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force,residence time and in vitro drug release.The in vitro drug release studies revealed that drug released for 8 h,which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.展开更多
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 thr...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.展开更多
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 indicat...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.展开更多
Posaconazole(PCZ)is a broad-spectrum anti-fungal drug approved by FDA and currently used off-label for the treatment of fungal keratitis(FK).Although ocular route serves as the most bioavailable route for treating FK,...Posaconazole(PCZ)is a broad-spectrum anti-fungal drug approved by FDA and currently used off-label for the treatment of fungal keratitis(FK).Although ocular route serves as the most bioavailable route for treating FK,delivery of PCZ to the eye remains a challenge due to poor permeation though the cornea and rapid elimination from the eye.Here we outline a comprehensive formulation development process,beginning with in silico studies,progressing through in vitro evaluations,and ultimately achieving therapeutic benefits in vivo.We report modified niosome-like surfactant vesicles,hereafter termed as NioTherms,formulated using a novel and simple heat-mix method,encapsulating PCZ for ocular administration in the form of an in situ gel.Excipient screening performed using in silico simulations highly correlate with in vitro studies(R^(2)=0.77),guiding optimization by Quality by Design(QbD)approach for encapsulating PCZ in NioTherms resulting in particles with an average size of 180.7±2.3 nm,zeta potential of +27.5±2.2 mV and entrapment efficiency of 87.6%±1.7%.A 2-fold increase in both mucin binding and cellular uptake indicates a functional role of positive surface charge in enhancingmucoadhesive properties of PCZ-NioTherms.In an in vivo murine ocular keratitis model,we demonstrate a 2-fold enhancement in trans-corneal permeability of PCZ-NioTherms and a 3-fold reduction in fungal burden compared to the control standard of care,the PCZ solution.Owing to a facile formulation process,we anticipate that PCZ-NioTherms would serve as a clinically translatable and patient compliant therapeutic intervention for treating FK.展开更多
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 dys...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.展开更多
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 ...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.展开更多
Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to t...Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties,therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available. A number of studies have underscored the relationship of subcutaneous injections with patient non-adherence, estimating that over half of insulin-dependent adults intentionally skip injections. The development of oral formulations has the potential to address some issues associated with non-adherence including the interference with daily activities, embarrassment, and injection pain. Oral delivery can also help to eliminate the adverse effects and scar tissue buildup associated with repeated injections. However, there are several major challenges associated with oral delivery of proteins and peptides, such as the instability in the gastrointestinal(GI)tract, low permeability, and a narrow absorption window in the intestine. This review provides a detailed overview of the oral delivery route and associated challenges. Recent advances in formulation and drugdelivery technologies to enhance bioavailability are discussed, including the co-administration of compounds to alter conditions in the GI tract, the modification of the macromolecule physicochemical properties, and the use of improved targeted and controlled release carriers.展开更多
Tizanidine hydrochloride(THCl)is an antispasmodic agent which undergoes extensive first pass metabolism making it a possible candidate for buccal delivery.The aim of this study was to prepare a monolayered buccal patc...Tizanidine hydrochloride(THCl)is an antispasmodic agent which undergoes extensive first pass metabolism making it a possible candidate for buccal delivery.The aim of this study was to prepare a monolayered buccal patch containing THCl using the emulsification solvent evaporation method.Fourteen formulations were prepared using the polymers Eudragit■ RS 100 or EudragitB RL 100 and chitosan.Polymer solutions in acetone were combined with a THCl aqueous solution(in some cases containing chitosan)by homogenization at 9000 rpm for 2 min in the presence of triethyl citrate as plasticizer and cast in novel Teflon molds.Physicochemical properties such as film thickness,in vitro drug release and in vitro mucoadhesion were evaluated after which permeation across sheep buccal mucosa was examined in terms of flux and lag time.Formulations prepared using a Eudragit■polymer alone exhibited sa tisfactory physicomechanical properties but lacked a gradual in vitro drug release pattern.Incorporation of chitosan into formulations resulted in the formation of a porous structure which did exhibit gradual release of drug.In conclusion,THCl can be delivered by a buccal patch formulated as a blend of Eudragit■ and chitosan,the latter being necessary to achieve gradual drug release.展开更多
基金This work was financially supported by the National Key Research and Development Program of China(2021YFA0909400)the National Natural Science Foundation of China(22105123,22305152)+3 种基金the Shanghai Rising-Star Program(23QA1408600),the Explorer Program of the Science and Technology Commission of Shanghai Municipality(21TS1400400)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2021QN35),the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20210900)the Foundation of National Infrastructures for Translational Medicine(Shanghai)(TMSK-2021-119)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20181704).
文摘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.
基金supported by the National Natural Science Foundation of China(No.81903811)China Postdoctoral Science Foundation(No.2021M690488)National TCM Multidisciplinary Interdisciplinary Innovation Team Project:Multidisciplinary Evaluation of Southwest Characteristic TCM Resources Multidisciplinary Interdisciplinary Innovation Team(No.ZYYCXTD-D-202209)。
文摘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.
基金This research is financially supported by the Natural Science Foundation of China(Grant No.81273446).
文摘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.
基金supported by RR college of Pharmacy affiliated to Rajiv Gandhi University of Health Sciences,Bangalore,India(Grant No.RRCP\PCEUTICS\IHR&D\231)
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.82101076,81771122,81970985)Key Research Program of Sichuan Science and Technology Department(No.2019YJ0147)Postdoctoral Research Foundation of China(No.2020M683334)。
文摘Oral and maxillofacial diseases are a group of high-incidence disorders that affect people’s life quality to a great extent,while the wet and highly movable environment of the related regions brings challenges to traditional therapies.Faced with the obstacles of insufficient adhesive strength and ensuing short drug retention time,conventional oral therapeutic agents often have difficulty in achieving their desired efficacy.Oral and maxillofacial wet-adhesive materials have the advantages of excellent wet environment retention,internal stability,plasticity,and clinical potential,thus have become a significant research direction in the field of oral related disorders healing.In the past decade,the development of oral adhesive materials with good wet adhesion has accelerated based on the chemical molecular interaction,physical interlocking,and biological adhesion mechanisms,including biomimetic-inspired materials,naturally derived polymer–based materials and adhesive electrospun fiber films.These fancy wet-adhesive materials can be used for oral mucosal drug delivery,oral vaccination,wound healing,and bone defects treatments.Despite their numerous novel applications,wet-adhesive materials in stomatology still face unresolved challenges from material and biological aspects.Here,advances in designs of oral and maxillofacial wetadhesive materials are reviewed in terms of design backgrounds,attachment mechanisms,and common classifications.Recent demonstrations of wet-adhesive materials for oral and maxillofacial region medical applications from drug delivery to multifunctional tissue treatments are presented.To conclude,current challenges and prospects on potential applications of oral and maxillofacial wet-adhesive materials are also briefly discussed.
文摘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.
文摘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.
文摘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 Ca<sup>2+</sup> 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.
文摘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.
文摘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].
基金the financial support provided by Thammasat University under the TU Research Scholar,Contract No.TP 2/68/2556
文摘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.
文摘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.
文摘The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis.The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment.The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method.Microcry stalline cellulose was used as the filler and its effect was also studied.The prepared dosage forms were evaluated for physicochemical properties,in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue.Tablets containing 50% of polymers(Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force,residence time and in vitro drug release.The in vitro drug release studies revealed that drug released for 8 h,which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.
文摘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.
文摘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.
文摘Posaconazole(PCZ)is a broad-spectrum anti-fungal drug approved by FDA and currently used off-label for the treatment of fungal keratitis(FK).Although ocular route serves as the most bioavailable route for treating FK,delivery of PCZ to the eye remains a challenge due to poor permeation though the cornea and rapid elimination from the eye.Here we outline a comprehensive formulation development process,beginning with in silico studies,progressing through in vitro evaluations,and ultimately achieving therapeutic benefits in vivo.We report modified niosome-like surfactant vesicles,hereafter termed as NioTherms,formulated using a novel and simple heat-mix method,encapsulating PCZ for ocular administration in the form of an in situ gel.Excipient screening performed using in silico simulations highly correlate with in vitro studies(R^(2)=0.77),guiding optimization by Quality by Design(QbD)approach for encapsulating PCZ in NioTherms resulting in particles with an average size of 180.7±2.3 nm,zeta potential of +27.5±2.2 mV and entrapment efficiency of 87.6%±1.7%.A 2-fold increase in both mucin binding and cellular uptake indicates a functional role of positive surface charge in enhancingmucoadhesive properties of PCZ-NioTherms.In an in vivo murine ocular keratitis model,we demonstrate a 2-fold enhancement in trans-corneal permeability of PCZ-NioTherms and a 3-fold reduction in fungal burden compared to the control standard of care,the PCZ solution.Owing to a facile formulation process,we anticipate that PCZ-NioTherms would serve as a clinically translatable and patient compliant therapeutic intervention for treating FK.
基金supported by the University of Wisconsin Carbone Cancer Center Research Collaborativethe Pancreas Cancer Task Force and the start-up package from the University of Wisconsin-Madison.
文摘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.
基金National Research Foundation of Korea,Grant/Award Numbers:2023-00208913,RS-2023-00208262。
文摘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.
基金supported in part by a grant from the National Institutes of Health (R01-EB-00246020)the Cockrell Family Regents Chair. Angela M.Wagner was supported by a National Science Foundation Graduate Research Fellowship (DGE-1610403)+1 种基金the S.E.S.H.A. Endowed Graduate Fellowship in Engineeringthe Philanthropic Educational Organization Scholar Award
文摘Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties,therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available. A number of studies have underscored the relationship of subcutaneous injections with patient non-adherence, estimating that over half of insulin-dependent adults intentionally skip injections. The development of oral formulations has the potential to address some issues associated with non-adherence including the interference with daily activities, embarrassment, and injection pain. Oral delivery can also help to eliminate the adverse effects and scar tissue buildup associated with repeated injections. However, there are several major challenges associated with oral delivery of proteins and peptides, such as the instability in the gastrointestinal(GI)tract, low permeability, and a narrow absorption window in the intestine. This review provides a detailed overview of the oral delivery route and associated challenges. Recent advances in formulation and drugdelivery technologies to enhance bioavailability are discussed, including the co-administration of compounds to alter conditions in the GI tract, the modification of the macromolecule physicochemical properties, and the use of improved targeted and controlled release carriers.
文摘Tizanidine hydrochloride(THCl)is an antispasmodic agent which undergoes extensive first pass metabolism making it a possible candidate for buccal delivery.The aim of this study was to prepare a monolayered buccal patch containing THCl using the emulsification solvent evaporation method.Fourteen formulations were prepared using the polymers Eudragit■ RS 100 or EudragitB RL 100 and chitosan.Polymer solutions in acetone were combined with a THCl aqueous solution(in some cases containing chitosan)by homogenization at 9000 rpm for 2 min in the presence of triethyl citrate as plasticizer and cast in novel Teflon molds.Physicochemical properties such as film thickness,in vitro drug release and in vitro mucoadhesion were evaluated after which permeation across sheep buccal mucosa was examined in terms of flux and lag time.Formulations prepared using a Eudragit■polymer alone exhibited sa tisfactory physicomechanical properties but lacked a gradual in vitro drug release pattern.Incorporation of chitosan into formulations resulted in the formation of a porous structure which did exhibit gradual release of drug.In conclusion,THCl can be delivered by a buccal patch formulated as a blend of Eudragit■ and chitosan,the latter being necessary to achieve gradual drug release.
