Bioadhesive Drug Delivery Systems Research Articles

Bioadhesive polymer in antifungal drug delivery for therapeutic treatment of candidiasis.

Candida species are the primary cause of candidiasis, a common yeast infection, with Candida albicans being the most prevalent pathogen. These infections often infiltrate the body through cutaneous and vaginal routes. Given the potential severity of some Candida infections, particularly invasive cases, there is a critical need for effective antifungal treatments. Controlled drug delivery strategies have been developed to achieve optimal release kinetics and precise targeting of active agents, especially in fungal infection therapeutics. Consequently, significant attention has been focused on exploring and utilizing bioadhesive polymers to enhance the performance of drug delivery systems for antifungal medications. Bioadhesive drug delivery systems aim to sustain the release of therapeutic agents, reducing the need for frequent dosing. This article provides a comprehensive review of scientific investigations into the use of antifungal drugs within bioadhesive drug delivery systems for treating candidiasis, locally and systemically. The evaluation covers the efficacy of these systems against candidiasis, factors affecting prolonged contact at the application site, and the underlying mechanisms of drug delivery.

Novel approaches of gastro retentive drug delivery system

Oral route of drug administration is the most convenient route and accepted route of drug delivery. It is probable that at least 90% of all the drugs given by oral route. There are different drug deliveries to cure the diseases through oral route. Among them Gastroretentive drug delivery system plays an important and significant role in novel drug delivery systems. The floating systems, bioadhesive drug delivery system, expandable drug delivery system, high density systems, effervescent systems (Gas Generating systems), non-effervescent systems etc are various approaches. The wide applications can be achieved through this delivery system are enhanced bioavailability, sustained drug delivery, site-specific drug delivery, absorption enhancement, mitigating adversity at colon etc. In addition to specified above, the advantages and disadvantages, drugs and polymers used and the method of evaluation is also summarized in this review.

Metronidazole Based Floating Bioadhesive Drug Delivery System for Potential Eradication of H. pylori: Preparation and In Vitro Characterization.

Metronidazole has the potential to produce local stomach specific action in order to treat Helicobacter pylori induced peptic ulcer disease. The current project executes the development of osmotically controlled bioadhesive metronidazole loaded effervescent floating tablets with optimized floating and swelling behavior. Direct compression technique was used to prepare the tablets. The designed formulations exhibited physico-chemical properties within acceptable optimum limits as per pharmacopeial requirements. The results of tablet floating studies revealed that all formulations, except F1 and F5, had good buoyancy characteristics (TFT > 12 h except F2 and F8 with TFT of 6 h). Formulation F2 containing guar gum in higher concentration with carbopol and formulation F8 containing guar gum in 50% decreased concentration in combination with HPMC and carbopol had enhanced FLT appreciably, with least TFT as compared to formulations F3, F4, and F6 (ANOVA; p ≤ 0.05). Formulation batches of F3, F4, and F6 exhibited appreciable FLT as well as TFT and were optimized formulations. Out of the above mentioned optimized batches, F4 and F6 formulations showed low FLT (4 and 5 s respectively). The results of the swelling study indicated a proportionate increase in the swelling index with increase in time. A significantly higher swelling ratio was found with formulation F6 and F4 compared with that of F7 and F8 (ANOVA; p ≤ 0.05). Additionally, the impact of pH change, agitational intensity, as well as increasing concentration of NaCl was investigated on drug release. It was observed that agitational intensity had no effect on drug release rate while increasing concentration of NaCl produced an increased drug release from the dosage form as compared to the drug release exhibited by the formulations in the absence of NaCl. Overall, this project could have valuable contribution in the fabrication of metronidazole loaded effervescent floating tablets. Gastro-retentive systems are expected to enhance local stomach specific action of anti H. pylori agents based on their buoyancy and swelling behavior.

Formulate gastroretentive floating bioadhesive drug delivery system of nizatidine by direct compression technique

Formulate gastroretentive floating bioadhesive drug delivery system of nizatidine by direct compression technique

Formulation and Evaluation of Vaginal Bioadhesive Drug Delivery System of Acyclovir

Acyclovir is an anti-viral, which has been used in the treatment of vaginal disorder. Acyclovir is almost completely absorbed after oral administration but has low bioavailability of about 10-15% because of first pass metabolism. As first pass metabolism removes approximately 85-90% of the drug, so for clinical efficacy of the drug it should be frequently administered. Hence an attempt has been made to produce sustained release dosage form of the acyclovir which can be specifically employed for the treatment of vaginal disordered by Herpes simplex virus. The Mucoadhesive tablets of acyclovir has been prepared by direct compression methods and evaluated for various parameter such as thickness, friability, hardness, drug content, weight variation, swelling index, surface pH, bioadhesive force, bioadhesive time, drug release etc. The kinetic data was applied to the optimized formulations. So formulation of acyclovir in a vaginal mucoadhesive tablet dosage form will decrease the frequency of administration, which can lead to an improvement in patient adherence and thereby improving its clinical efficacy.

Formulation and Characterization of Eplerenone Mucoadhesive Buccal Tablets

Mucoadhesive drug release system is a preferably unidirectional release system where mucosal epithelial exterior is enclosed by the mucus deposit that interacts with the bio-adhesive drug delivery system and swelling time of the buccal dosage form which is amplified by mucin molecules at the location of administration. Eplerenone is an Anti-hypertensive drug that undergoes hepatic first pass metabolism and shows 69% of bioavailability. In order to bypass the hepatic first pass metabolism the drug is designed to be delivered through buccal cavity to avoid the first pass metabolism. Eplerenone buccal tablets were formulated by using direct compression method with different polymers like HPMC K 100M, Carbopol 934P, Carbopol 974P, Xantham Gum, Eudragit L100 and NaCMC in various concentrations and compositions. Incompatibility complications were not observed from the FTIR spectrums. The formulated and prepared buccal solid dosage forms were evaluated for pre-compressions and post- compression parameters such as hardness, weight variation, thickness, friability, surface pH, swelling index, in-vitro dissolution studies, drug content uniformity, mucoadhesion strength and mucoadhesion time. Evaluation results of formulation F12 are proven to be the optimal formulation showing highest mucoadhesion time, mucoadhesion strength and in-vitro drug release for prolonged period of time about 8 hours. Eplerenone is best delivered through buccal drug delivery system to enhance its oral bioavailability and bypass the hepatic first pass metabolism.

In vivo, ex vivo and in vitro Mucoadhesive Strength Assessment of Potential Pharmaceutical Bio-resource Polymer from Diospyros melonoxylon Roxb seeds

In this study, an oral bio-based mucoadhesive polymer was developed from Diospyros melonoxylon Roxb (Ebenaceae) seed mucilage and evaluated for mucoadhesive strength. The mucilage showed shear stress results (0.140 ± 0.0007N), with comparable adhesiveness to HPMC E5 (0.098 ± 0.0008N). Force of adhesion required to detach the seed mucilage and HPMC E5 tablets from the mucin of intestinal tissue were 0.0509 ± 0.0007 (N) and 0.0049 ± 0.0006 (N). Seed mucilage revealed significant higher detachment time, erosion time, in vitro wash off time and ex vivo residence compared to HPMC E5 and lactose tablets (p<0.01). In vivo test indicated that seed mucilage tablets possessed good mucoadhesive strength compared to HPMC E5 and resisted disintegration for ≤ 8 h. The swelling index and wetting time showed comparable results between the mucilage and synthetic polymer tablets. Mucilage demonstrated high moisture absorption, percentage hydration, and matrix erosion of 20.0 ± 0.037, 53.66 ± 0.127, and 20.00 ± 0.077 compared to HPMC E5 10.0 ± 0.079, 36.00 ± 0.089, and 1.26 ± 0.085. The mucoadhesive properties of seeds mucilage were comparable to guar gum and HPMC E5. Thus, seed mucilage of D. melonoxylon can be exploited for usage as pharmaceutical excipient in oral bioadhesive drug delivery systems.

Interpolyelectrolyte Complexes Based on Eudragit® Copolymers as Carriers for Bioadhesive Gastroretentive Metronidazole Delivery System

Introduction. There are a number of drugs, the absorption zone of which is the upper region of the gastrointestinal tract (GIT) – the stomach and duodenum. To increase bioavailability, gastroretentive (intragastric) systems for the controlled drug delivery are being developed. To date, there are various approaches to ensure intragastric drug delivery. One of the most promising approaches is the use of excipients with bioadhesive properties, both individually and in combination with other types of gastroretentive systems.Aim. Development and research of new carriers for gastroretentive bioadhesive drug delivery systems based on interpolyelectrolyte complexes (IPEC) with the participation of chemically complementary poly(meth)acrylates of the Eudragit®.Materials and methods. The study of swelling ability was carried out in a medium of 0.1 M hydrochloric acid solution (pH 1.2) at a temperature of 37 ± 0.5 °C for 6 hours. The study of the release of metronidazole (MZ) from matrices based on the corresponding IPEC was performed on a DFZ II instrument (ERWEKA, Germany) according to the Flow Trough Cell method in 0.1 M HCl medium, pH 1.2, flow rate 4 ml/min in a closed cycle within 6 hours. The amount of released MZ was estimated by UV spectrophotometry on a Lambda 25 instrument (PerkinElmer, USA) at a wavelength of 274 nm. IPEC adhesion was studied using a TA.XTplus texture analyzer (Stable Micro Systems, UK).Results and discussion. Matrices based on IPEC 1 were disintegrated after being in a medium with a pH of 1.2 for 4 hours, matrices based on IPEC 4 were dissolved in an acidic medium for 3 hours. At the same time, matrices based on IPEC 2 and IPEC 3 retain their shape throughout the experiment and are characterized by rather high values of the degree of swelling. IPEC samples are characterized by higher adhesion performance compared to individual copolymers. The release of metronidazole from matrices based on IPEC 1 occurs in accordance with Fick's law of diffusion; from the matrix based on IPEC 4, MZ is released according to the anomalous transport mechanism.Conclusion. IPEC 3 is promising for use as carrier for gastroretentive bioadhesive systems of controlled delivery of metronidazole.

A Bioadhesive Nanoplatform Enhances the Permeation of Drugs Used to Treat Diabetic Macular Edema

The management of diabetic macular edema (DME), a condition that leads to an irreversible and severe visual impairment, remains a substantial challenge worldwide. In this study, we developed a bioadhesive nanoplatform with enhanced drug penetration to explore alternative treatment modalities for DME. This nanoparticulate formulation consisted of a sequence of an amphiphilic phenylboronic acid-based block and random glycopolymer with a high loading capacity for dexamethasone (DEX) of up to 20% and sustained drug release in vitro at a clinically relevant dose. The bioadhesive nanocarriers penetrated the sclera and choroid and were distributed in the retina under the action of phenylboronic acid to further promote drug permeation and retention in target lesions. The pathological analysis, electroretinography examination and immunofluorescence staining revealed that the nanoformulation of DEX much more markedly reduced the symptoms of and inflammation associated with DME than the drug alone, without affecting the function of the retina. Bioadhesive drug delivery systems are expected to be a feasible approach to treat DME and other fundus diseases.

Bioadhesive or Mucoadhesive Drug Delivery System: A Potential Alternative to Conventional Therapy

The term bioadhesive describes materials that bind to biological substrates, such as mucosal membranes and in bioadhesive drug delivery systems, the term bioadhesion is used to describe the bonding or adhesion between a synthetic or natural polymer and soft tissues such as epithelial cells. The bioadhesive drug delivery formulation highlights the fact that readily accessible sites are utilized with the eye, oral cavity and vegina being targeted. The GI tract and the nasal cavity have also been extensively examined as a site for bioadhesive drug delivery. The term mucoadhesion is the subgroup of bioadhesion and in the mucoadhesion formulation attaches with the mucus membrane. The mucoadhesion can be defined as the adhesion between the two materials in which one is biological material and other one is polymeric materials with the help of interfacial forces to increase the residence time. Over the past few decades, mucosal drug delivery has received a great deal of attention. The mucoadhesion drug delivery system is better than the traditional drug delivery systems. Mucoadhesion is a useful strategy for drug delivery systems, such as tablets, patches, gels, liposomes, micro/nanoparticles, nanosuspensions, microemulsions and colloidal dispersions. The mucoadhesion bypasses the first pass metabolism and used for localized delivery of biomolecules such as peptides, proteins and oligonucleotides. Mucoadhesion drug delivery system engages much attention due to their benefits such as prolong retention time, fast uptake and increased bioavailability of active substance. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, theories of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, mucoadhesive polymers and herbal drugs. Keywords: Bioadhesive, bioadhesive drug delivery, Mucoadhesion, Patches, Herbal drugs

Formulation Development and Evaluation of Gastro Retentive Bio Adhesive Drug Delivery System for Moxifloxacin. HCl

Formulation Development and Evaluation of Gastro Retentive Bio Adhesive Drug Delivery System for Moxifloxacin. HCl

Cellular uptake and transport characteristics of chitosan modified nanoparticles in Caco-2 cell monolayers

The bioadhesive drug delivery systems, chitosan modified nanoparticles, can efficiently adhere to mucosal surface of gastrointestinal tract and prolong residence time but a deeper understanding about its cellular uptake and transport is still lack. Hence, the present study was designed to compare the process of uptake and transport between chitosan modified and unmodified PLGA nanoparticles. Chitosan modified nanoparticles were formulated by classic and chemical methods. The morphology and modification potency were characterized by zeta potential, FTIR, DSC, XPS and TEM. Coumarin-6 load chitosan modified nanoparticles were incubated with Caco-2 cells to study the process of uptake and transport. The kinetic of cellular uptake for chitosan modified and unmodified nanoparticles was time- and concentration-dependent endocytosis but the cellular uptake efficiency of modified nanoparticles was significantly higher than that of unmodified one within the high concentration range (25.0–100.0 μg/mL). The modified nanoparticles underwent clathrin-mediated endocytosis and macropinocytosis but unmodified nanoparticles occurred a clathrin-mediated endocytosis. Both types of nanoparticles can increase caulophine with low solubility and poor stability transmembrane transport and the modified nanoparticles exhibited a better transcellular permeability. Therefore, the chitosan modified nanoparticles showed significantly improved cellular uptake and transcellular transport and a potential improvement in the efficacy of oral drug delivery.

AN OVERVIEW ON INTRANASAL DRUG DELIVERY SYSTEM: RECENT TECHNIQUE AND ITS CONTRIBUTION IN THERAPEUTIC MANAGEMENT

Nasal drug administration has been used as an important another route for the systemic availability of drugs. Intranasal route has large surface area, high total blood flow, avoidance of first-pass metabolism, porous endothelial membrane, and ready accessibility. For nasal route administration various drugs including peptide and protein drugs, for systemic medication has been widely used in recent few years. This review article highlights the importance, strategies and advantages of the nasal drug delivery systems. Various methods are discussed here for increasing the residence time of drug formulations in the nasal cavity, for improving nasal drug absorption. In this review article we discuss the effects of bioadhesive drug delivery systems on nasal drug administration. Drug delivery systems (such as nanoemulsion, microspheres, liposome and gels) have good bioadhesive characteristics which swell easily when in contact with the nasal mucosa. These types of drug delivery systems protect the drug from enzymatic degradation in nasal secretions and also control the rate of drug clearance from the nasal cavity.

A Review on Mucoadhesive Drug Delivery Systems

This article gives a brief idea about Bioadhesive drug delivery systems based on hydrogels to biological surfaces that are covered by mucus. Bioadhesion is an interfacial phenomenon in which two materials, at least one of which is biological are held together by means of interfacial forces, when the associated biological system is mucous. These systems remain in close contact with the absorption tissue, the mucous membrane, releasing the drug at the action site leading to a bioavailability increase and both local and systemic effects. Several in vitro and in vivo methodologies are proposed for studying its mechanisms. Oral mucoadhesive micro carriers were having potentiality for controlling and extending release profile so as to improve performance and patient compliance. The aim of this study was to review the mechanisms and theories involved in mucoadhesion, as well as to describe the most-used methodologies and polymers in mucoadhesive drug delivery systems.

Rheological and mucoadhesive properties of polysaccharide from Bletilla striata with potential use in pharmaceutics as bio-adhesive excipient

This study described the rheological and mucoadhesive properties of one natural water-soluble polysaccharide from Bletilla striata (BSP). The rheological characteristics of BSP in aqueous solutions and BSP mixed with other polymers were investigated under various conditions, including concentration, temperature, pH, and salt addition. Viscometric studies and ex vivo mucoadhesion tests were also conducted to examine the mucoadhesive properties of BSP. Results indicated that BSP behaved as a shear-thinning fluid at various concentrations, and its viscosity decreased at high temperatures. The viscous flow properties of the BSP mixtures changed at high pH (>5.0). Conversely, the viscosity of the BSP solutions was slightly affected by electrolytes. The viscosities of the BSP mixtures with four other commonly used polymers (sodium alginate, sodium carboxymethyl cellulose, hypromellose, and chitosan) were enhanced. The synergistic viscosity of BSP/mucin mixtures increased as BSP concentrations increased, and the maximum value was observed in the SIF medium without enzymes. The adhesive abilities of 5.0% and 10.0% BSP were almost equivalent to that of 0.5% sodium alginate, suggesting that BSP exhibited a certain mucoadhesive property, although it was weaker than that of the other commonly used mucoadhesive materials. BSP showed potential for pharmaceutical excipient applications in bioadhesive drug delivery systems.

Preparation and Evaluation of a Bio-Erodible Bio-Adhesive Drug Delivery System Designed for Intraoral Extended Release of Flurbiprofen: In Vitro and In Vivo Assessments

Site-specific drug delivery for the local treatment of the diseases in the oral cavity is far superior to the systemic administration, for both safety and efficacy reasons. This study presents the design and development of an innovative bio-adhesive delivery system (BDS) based on a bio-erodible semi-interpenetrating polymeric network (semi-IPN) for intraoral extended release of flurbiprofen (FBP). A unique combination of hydrolyzed gelatin (HG) cross-linked by tannic acid (TA) and Eudragit S, as the linear polymer, was used to compose the structure of the semi-IPN. The effect of structural factors, associated with the composition of the semi-IPN, on the release profile of FBP from the system was assessed using an in vitro dissolution method. The release rate of the drug in the oral cavity of healthy volunteers was also studied. The degree of cross-linking of HG and the weight ratio between the cross-linked polymer and the linear polymer were found to be crucial factors affecting the release profile of FBP from the system. Likewise, the presence of a high concentration of plasticizer was essential for achieving a proper flexibility of the system as proved by a DSC method. The in vivo tests demonstrated a disparity between the volunteers in the FBP concentration found in the saliva, especially after 120 min post-administration of BDS. Both f1 and f2 tests indicated that the packaged BDS can be absolutely stable for at least 6 months at 30 °C.

Evaluation of Ciprofloxacin Floating-Bioadhesive Tablet Formulated with Okra Gum as Multifunctional Polymer

Floating drug delivery systems and bioadhesive drug delivery systems are gastroretentive systems for increasing gastric residence time to obtain improved drug bioavailability. This study was to evaluate the floating and bioadhesive characteristics of Ciprofloxacin tablets formulated with Abelmoschus esculentus gum (okra gum).Okra gum was extracted and granules were prepared using the extracted Okra gum as well as sodium alginate and HPMC at concentrations of 2.5, 5 and 10 % w/w. Ciprofloxacin floating bioadhesive (CFB) tablets were evaluated for hardness, friability, in vitro buoyancy test, ex vivo bioadhesion test and drug release profiles. The floating lag time (FLT) and total floating time (TFT) for CFB tablets formulated with 10% w/w okra gum were 5.7 minutes and 8 hours respectively while the bioadhesive force was 1.324 N. Formulations of ciprofloxacin tablets containing admixtures of okra gum and sodium alginate or HPMC resulted in significant decrease (p < 0.05) in the floating lag times (≤ 3.1 minutes) and significant increase (p < 0.05) in total floating times (> 12 h). The bioadhesive force for CFB tablets containing admixtures of okra gum and sodium alginate or HPMC gave higher values in the range of 1.766 – 2.207 N. The in vitro release profiles for CFB tablets formulated with okra gum alone did not show sustained release below 10 % w/w. Batches FB10 and FB11 containing admixtures showed sustained release with maximum release of 86% at maximum time of 9 h. The dissolution profiles of tablets from batches F10 and F11 compared favourably with the profile for the commercial brand of floating ciprofloxacin tablet, MF. From the study Okra gum has shown to possess good floating and bioadhesive properties and may be utilized in the formulation gastro-retentive dosage form of ciprofloxacin which can possibly be harnessed as a targeted site-specific delivery system in the eradication of Helicobacter pylori in gastric ulcer disease as well as in the treatment of Salmonella typhi induced enteric fever.

Bio-adhesive drug delivery system and its application in traditional Chinese medicine

Bio-adhesive drug delivery system (BDDS) is a novel drug delivery system, which can prolong the retention time of the preparation, improve the stability of the drug, and improve the mucosa absorption and the targeting of the drug. With the development of polymer materials over the past 30 years, BDDS made a great progress. This paper reviews the muco-adhesion theory, adhesive materials, and methods to evaluate muco-adhesive properties and applications in traditional Chinese medicine according to domestic and foreign literatures, in order to provide new ideas for further studies.

A Review on Promising Novel Drug delivery System - Bioadhesive Drug Delivery System

Bioadhesive drug delivery system has gained sufficient attention of researchers not only due to their enormous advantages but also feasibility of formulation and patient compliance.In this review an effort was made to describe aspects of bioadhesive films, their preparation methods,polymer used in the formulation of this type of drug delivery system, different mechanism of how plasticizer work in drug delivery films and different evaluation parameters of this type of formulation so that this can be further studied and formulated with wide spectrum drug by checking suitability of the formulation with the active pharmaceutical ingredient.

Poly(vinyl methyl ether/maleic anhydride)-Doped PEG-PLA Nanoparticles for Oral Paclitaxel Delivery To Improve Bioadhesive Efficiency.

Bioadhesive nanoparticles based on poly(vinyl methyl ether/maleic anhydride) (PVMMA) and poly(ethylene glycol) methyl ether-b-poly(d,l-lactic acid) (mPEG-b-PLA) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4.0%. The nanoparticles were uniform and spherical in shape and exhibited a sustained drug release compared with Taxol. m-NPs also exhibited favorable bioadhesive efficiency at the same time. Coumarin 6 or DiR-loaded nanoparticles with/without PVMMA (C6-m-NPs/DiR-m-NPs or C6-p-NPs/DiR-p-NPs) were used for cellular uptake and intestinal adhesion experiments, respectively. C6-m-NPs were shown to enhance cellular uptake, and caveolae/lipid raft mediated endocytosis was the primary route for the uptake of the nanoparticles. Favorable bioadhesive efficiency led to prolonged retention in the intestine reflected by the fluorescence in isolated intestines ex vivo. In a ligated intestinal loops model, C6-m-NPs showed a clear advantage for transporting NPs across the mucus layer over C6-p-NPs and free C6. The apparent permeability coefficient (Papp) of PTX-m-NPs through Caco-2/HT29 monolayers was 1.3- and 1.6-fold higher than PTX-p-NPs and Taxol, respectively, which was consistent with the AUC0-t of different PTX formulations after oral administration in rats. PTX-m-NPs also exhibited a more effective anticancer efficacy, with an IC50 of 0.2 ± 1.4 μg/mL for A549 cell lines, further demonstrating the advantage of bioadhesive nanoparticles. The bioadhesive nanoparticles m-NPs demonstrated both mucus permeation and epithelial absorption, and thus, this bioadhesive drug delivery system has the potential to improve the bioavailability of drugs that are insoluble in the gastrointestinal environment.