A Review on Multi-functional Chitosan Derivatives for Diabetes Management: Mucoadhesive Drug Delivery and Diabetic Wound-healing Applications

Since the early 1980s the concept of mucoadhesion has gained considerable interest in pharmaceutical technology. The various advantages associated with these systems made buccal drug delivery as a novel route of drug administration. It prolongs the residence time of the dosage form at the site of application. These systems remain in close contact with the absorption tissue, the mucous membrane, and thus contribute to improved and/or better therapeutic performance of the drug and of both local and systemic effects. This review highlights the anatomy and structure of oral mucosa, mechanism and theories of mucoadhesion, factors affecting mucoadhesion, characteristics and properties of desired mucoadhesive polymers, various types of dosage forms, and general considerations in design of mucoadhesive buccal dosage forms, permeation enhancers, and evaluation methods. Over the past few decades the mucoadhesive buccal drug delivery system has received a great deal of attention to develop mucoadhesive dosage forms to enable the prolonged retention at the site of action, providing a controlled release of drug for improved therapeutic outcome. Mucoadhesive drug delivery gives facility to include a permeation enhancer/enzyme inhibitor or pHmodifier in the formulation and versatility in designing as multidirectional or unidirectional release systems for local and systemic action. Local delivery to tissues of the oral cavity has a number of applications, including treatment of local conditions such as periodontal disease, bacterial and fungal infections, and aphthous stomatitis and vesiculo bullous diseases. For the treatment of chronic diseases, the mucoadhesive buccal drug delivery system allows easily accessibility and is generally well-accepted for administeringdrugs by systemic action.

Natural Polysaccharides in Drug Delivery and Biomedical Applications

The two major problems in the development of new drugs are low aqueous solubility and low oral bioavailability. Although, drug delivery via oral route is most preferred for years but it also has some drawbacks. Various techniques for improving the solubility have been developed, however the success of these techniques depends on the physical and chemical properties of the drug under development. In recent years, mucoadhesive drug delivery gained high popularity in comparison to other routes of drug delivery as it can circumvent the drawbacks of conventional delivery system such as first pass metabolism, enzymatic degradation, GI toxicity of some drugs, instability in acidic or alkaline environment and poor bioavailability. Various mucoadhesive dosage forms have been developed recently including tablets, patches, films, ointments, gels etc. The objective of current review is to provide a comprehensive overview of mucoadhesive drug delivery including the mechanism and theories behind mucoadhesion, factors affecting mucoadhesion, different dosage forms, polymers used in mucoadhesive formulations, characterization techniques, marketed products and current scenario & future challenges. Keywords: Mucoadhesion, Buccal mucosa, Mucoadhesive drug delivery, Mucoadhesive polymers, Mucus membrane, Patents

Mucoadhesive drug delivery systems have emerged as a promising approach to enhance the efficacy and specificity of drug administration. In recent years, significant advancements in this domain have expanded the possibilities of targeted drug delivery to mucosal surfaces, revolutionizing the Pharmaceutical field. The utilization of novel mucoadhesive polymers and nanoparticles has paved the way for controlled and sustained drug release, overcoming the limitations of conventional dosage forms. By exploiting the adhesive properties of these formulations, drug bioavailability has been substantially improved, while the extended residence time at the target site allows for optimized therapeutic outcomes. Such advancements have particularly proven beneficial for delivering a diverse range of therapeutics, including vaccines, peptides, proteins, and nucleic acids. Furthermore, the integration of advanced nanotechnology and bioengineering techniques has led to the development of mucoadhesive platforms with enhanced stability, biocompatibility, and tailored release profiles. Recent advancements in mucoadhesive drug delivery hold immense promise for personalized and targeted therapeutic interventions. The continuous evolution of this field is likely to result in more effective and patient-friendly drug delivery solutions, ultimately improving patient compliance and healthcare outcomes. By addressing the remaining challenges, mucoadhesive drug delivery can be expected to play a vital role in shaping the future of Pharmaceutical research and clinical practice. . This chapter aims to provide an overview of the recent developments in mucoadhesive drug delivery, highlighting key research findings and technological innovations.

Introduction: In recent years, mucoadhesive topical application of mucous membrane has gained considerable interest among formulation researchers in advanced drug delivery systems. It has been identified as a potential route for both local and systemic drug delivery. A mucoadhesive agent is usually incorporated in the formulation to overcome the disadvantages associated with the conventional topical formulation. These disadvantages include low residence time of the medication on the site of application due to tongue movement and salivary washout in the intraoral formulation, mucociliary clearance in the intranasal application, and rapid precorneal elimination in the intraocular formulation. Carbomer or known as Carbopol is a mucoadhesive polymer that is widely studied for topical delivery of pharmaceutical agents to the mucous membrane. The use of Carbopol and its advantages in the mucoadhesive topical application has gained considerable interest with several published studies and is available in various grades. In this study, a systematic review was performed on the available literature that investigates the Carbopol application in mucoadhesive topical drug delivery. Method: A systematic searching strategy was performed in Scopus, ProQuest, and PubMed databases using predetermined search strings. A total of 778 articles were retrieved, however, only 25 articles met the inclusion criteria and were used for data synthesis. Results: The results showed that incorporation of Carbopol as mucoadhesive polymer hold multiple advantages in drug delivery namely excellent mucoadhesion effect, the prolonged residence time of the formulation, enhanced drug permeation, prolonged release of drug, pseudoplastic behaviour of the formulation, pH compatibility with all mucosal site, and biocompatible. Conclusion: This suggests that the incorporation of Carbopol can be an effective mucoadhesive agent for topical drug delivery systems.

Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive 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.

Thiol-modified nanoparticles have potential applications in mucoadhesive drug delivery and have been examined in this regard for topical ocular delivery. In this paper we provide a simple method for the synthesis of a dithiol terminated amphiphilic diblock copolymer. Bidentate dithiol-poly(ethylene glycol)-poly(d,l-lactide) (SH2-PEG-PDLLA) was synthesized and micelles with dithiol-containing coronas were prepared from this block copolymer via the emulsion method. In vitro release studies indicated that the presence of the thiol groups at the surface did not affect the rate of release of dexamethasone, used as a representative ocular drug. The micelles also showed low cytotoxicity to human corneal epithelial cells (HCEC) and murine fibroblast cells (3T3 cells). A hydrophobic red fluorophore, Nile red, was loaded into the core of micelles and confocal microscopy was used to study HCEC uptake and retention of the micelles. The micelles were rapidly endocytosed by the HCEC, with intracellular micelle levels remaining unchanged with incubation times from 5 to 120 min. Interestingly, Nile red was eliminated significantly more slowly from HCECs treated with the thiolated micelles. These results suggest that these dithiolated micelles may be effective for topical ocular drug delivery.

ABSTRACTHydrogels with mucoadhesive properties offer significant potential for drug delivery due to their tunable physicochemical characteristics and sustained drug release capabilities. This research investigates polymer hydrogels synthesized via thiol‐ene click reactions between pentaerythritol tetrakis(3‐mercaptopropionate) (PEMP) and polyethylene glycol diacrylate (PEGDA), exploring their potential as effective mucoadhesive and antimicrobial drug delivery systems. Sol–gel analysis revealed that gel formation efficiency depends on the acrylate‐to‐thiol ratio, with stoichiometric formulations yielding higher gel fractions. FTIR spectroscopy and elemental analysis confirmed the chemical composition of these hydrogels, showing the presence of residual CC bonds and a decrease in thiol group content with increasing PEGDA concentration. The mechanical properties were superior in hydrogels prepared using stoichiometric (1:1) ratios of the reagents, while mucoadhesiveness—tested on ovine vaginal tissue—was enhanced in samples with higher thiols‐bearing PEMP content. Drug loading efficiency and release kinetics were evaluated for clindamycin phosphate and clotrimazole. Hydrophilic gels showed greater clindamycin loading and more sustained release compared to clotrimazole. Antimicrobial testing demonstrated that clindamycin‐loaded hydrogels exhibited strong antibacterial activity against Staphylococcus aureus . Clotrimazole‐loaded hydrogels showed less pronounced antifungal effects against Candida albicans . These findings highlight the applicability of PEGDA‐PEMP hydrogels for mucoadhesive drug delivery and antimicrobial applications.

Chapter 9 - Chitosan as mucoadhesive polymer in drug delivery

Innovations in pharmaceutical research are striving for designing newer drug therapies to eradicate deadly diseases. Strategies for such inventions always flourish with keys and objectives of minimal adverse effects and effective treatment. Recent trends in pharmaceutical technology specify that mucoadhesive drug delivery system is particularly appropriate than oral control release, for getting local systematic delivery of drugs in GIT for an extended interval of time at a predetermined rate. However, it is somehow expensive and unpleasant sensation for some patients, but still it is needful for getting short enzymatic activity, simple administration without pain and evasion of fast pass metabolism. Usually the vehicles employed in drug delivery of mucoadhesive system have a significant impact that draws further attention to potential benefits like improved bioavailability of therapeutic agents, extensive drug residence time at the site of administration and a comparatively faster drug uptake into the systemic circulation. The drug release from mucoadhesive multiparticulates is contingent on several types of factors comprising carrier need to produce the multiparticles and quantity of medication drug contained in them. Mucoadhesion is characterized by selected theories and mechanisms. Various strategies emergent in mucoadhesive multiparticulate drug delivery system (MMDDS) by in-vitro as well as ex-vivo description and characterization are also critically discussed. Apart from these, the primary focus during this review is to highlight current patents, clinical status, and regulatory policy for enhancement of mucoadhesive multi-particulate drug delivery system in the present scenario.

Chondroitin sulfate (CS), a naturally occurring glycosaminoglycan, is renowned for its biocompatibility, biodegradability, and considerable role in wound healing and drug delivery applications. In wound healing, CS fosters tissue regeneration by augmenting cell signaling, extracellular matrix remodeling, and accelerating tissue repair. As a drug delivery system, CS acts as an adaptable carrier, improving stability, bioavailability, and controlled release of therapeutic agents. Its ability to form hydrogels and nanoparticles enables prolonged, site-specific drug delivery, ensuring targeted therapeutic action at injury sites. Recent advancements have focused on CS-based formulations for chronic wound treatment, emphasizing its role in tissue regeneration and faster healing. The integration of CS with biomaterials like collagen and hydroxyapatite further optimizes therapeutic outcomes. In addition to CS, chondroitinase ABC (chABC) has gained attention for its potential in wound healing and drug delivery. chABC, an enzyme that degrades chondroitin sulfate chains, promotes tissue repair by breaking down inhibitory extracellular matrix components and promoting cell migration. The combination of CS and chABC could offer synergistic effects, enhancing wound healing and drug delivery efficiency. Challenges remain in optimizing formulations for clinical use, including stability, scalability, and regulatory issues, but the future potential for CS and chABC in therapy is significant.

Background:The drug delivery across buccal mucosa is a very interesting option for the treatment of various oro-mucosal disorders such as aphthous stomatitis, periodontitis, gingivitis, toothache, periodontitis, and sjorgensen syndrome. But it is quite difficult because of target site movements, limited area for drug absorption, drinking of fluids, intake of food and saliva flow at regular intervals, contributing to poor retention and sub-therapeutic level of drug at the target site. Due to this, the mucoadhesive buccal drug delivery system has gained a great deal of attention among the various scientists and researchers over the last two decades.Methods:Mucoadhesion is a process of attachment between the natural or synthetic macromolecule and mucosal epithelial surface with the aid of interfacial attractive forces. The process of mucoadhesion has been extensively encouraged by the utilization of mucoadhesive polymers within the formulation that on contact with salivary fluid swells and adheres to buccal epithelium membrane, thus prolonging the drug release, retention time and improving therapeutic performance in case of oral diseases. The present review tries to cover the basic anatomy and structure of oral mucosa, pathways of drug absorption, the theory of mucoadhesion, mechanisms involved in mucoadhesion and various factors affecting mucoadhesion.Results:It highlights the properties of mucoadhesive polymers in drug delivery along with various dosage forms such as mucoadhesive tablets, films, patches, gels, and pastes. Furthermore, it also sheds light on the recent developments made in the field of mucoadhesive buccal drug delivery system that reflects the potential of this system for the effective treatment of oro-mucosal disorders.Conclusion:It can be concluded that the mucoadhesive buccal drug delivery system has great potential in the near future for treating oro-mucosal disorders.

Thiolated polymers as mucoadhesive drug delivery systems

Carboxylate embedded metal organic frameworks for potential applications in drug delivery and controlled release

In the past several decades, various types of nanostructured biomaterials have been developed. These nanostructured biomaterials have promising applications in biomedical fields such as bone repair, tissue engineering, drug delivery, gene delivery, antibacterial agents, and bioimaging. Nanostructured biomaterials with high biocompatibility, including calcium phosphate, hydroxyapatite, and calcium silicate, are ideal candidates for drug delivery. This review article is not intended to offer a comprehensive review of the nanostructured biomaterials and their application in drug delivery but rather presents a brief summary of the recent progress in this field. Our recent endeavors in the research of nanostructured biomaterials for drug delivery are also summarized. Special attention is paid to the synthesis and properties of nanostructured biomaterials and their application in drug delivery with the use of typical examples. Finally, we discuss the problems and future perspectives of nanostructured biomaterials in the drug delivery field.