Chemical modification of chitosan to improve mucoadhesion for drug delivery

Vanukuru, S. (2025) Chemical modification of chitosan to improve mucoadhesion for drug delivery. PhD thesis, University of Reading. doi: 10.48683/1926.00130832

Abstract/Summary

This thesis focuses on the chemical modification of chitosan to enhance its residency time in the nasal cavity, thereby improving its effectiveness as a mucoadhesive drug delivery system. The research investigates the synthesis of chitosan derivatives through N-acylation using anhydrides and acyl chlorides and evaluates how these modifications enhance the mucoadhesive properties and retention of chitosan within nasal mucosa. A thorough understanding of the principles of mucoadhesion is explored, with an emphasis on developing formulations that can significantly enhance drug retention and absorption across mucosal surfaces, offering promising advancements in transmucosal drug delivery. The work described in the thesis can be broadly divided into three sections. Chapters 1,2 & 3 focus on the brief introduction and background to work. Chapter 4 & 5 focus on synthesis of novel chitosan derivatives, characterising them and exploring their potential as mucoadhesive drug delivery system with chapter 6 concluding this work. The first chapter introduces the history of transmucosal drug delivery, tracing its evolution from early methods to its current state. It then presents the concept of mucoadhesion, exploring various theories, including electronic, adsorption, wetting, and diffusion, which explain how polymers bond to mucosal tissues. This chapter lays the foundation for understanding the broader context and scientific principles that underpin the rest of the thesis. Chapter 2 focuses on various mucosal drug delivery systems, examining the physiological characteristics of different transmucosal tissues and the barriers that must be addressed for effective drug delivery. It explores the challenges posed by these barriers, such as limited absorption and retention time, and reviews modern strategies to overcome them. These include the use of nanoparticles, bioadhesive polymers, and other innovative approaches designed to enhance drug efficacy and adhesion to the mucosal surface. Additionally, various drug delivery strategies, such as tablets, suppositories, gels, and liquids, are discussed as potential methods for administering drugs through mucosal routes. By covering current technologies and approaches, this chapter sets the foundation for the experimental work presented in later chapters. Chapter 3 is a comprehensive review of chitosan, focusing on its potential in pharmaceutical applications. The chapter begins by outlining the production of chitosan, its chemical structure, and the properties that make it an attractive polymer for drug delivery, particularly its biocompatibility and mucoadhesive capabilities. The pharmaceutical applications of chitosan are then discussed, with an emphasis on chitosan-based products in development or currently in the market for mucoadhesive drug delivery systems. However, the chapter also identifies significant challenges that hinder the commercial use of chitosan, such as regulatory barriers and production difficulties. Despite these challenges, the chapter highlights the opportunities for future development of chitosan-based products. The fourth chapter explores the modification of chitosan with methacrylic anhydride and crotonic anhydride to enhance its mucoadhesive properties. The chapter outlines the synthesis of these derivatives and describes the methods used to characterise the modified chitosan derivatives using 1H NMR and FTIR. This is followed by ex vivo testing for nasal retention, using texture analysis, fluorescent imaging, and wash-off studies to assess the performance of spray-dried microparticles. In addition to these physical tests, toxicological studies were conducted using planaria and in vitro cell lines to evaluate the safety and biocompatibility of the modified chitosan derivatives. This chapter provides essential experimental evidence supporting the improved mucoadhesive properties of synthesised chitosan derivatives. Chapter 5 focuses on the design and evaluation of mucoadhesive nanoparticles, which were created by modifying chitosan with acryloyl chloride and methacryloyl chloride. The synthesis and characterisation of these derivatives are described, including the formation of nanoparticles, which were thoroughly analysed. The chapter then details the evaluation of the nanoparticles' mucoadhesive properties through fluorescent imaging and wash-off tests. Toxicological studies were also conducted using planaria and greater wax moth larvae to assess the safety of these nanoparticles. Finally, carbamazepine, an anti-epileptic drug, was encapsulated within the nanoparticles, and the entrapment efficiency was measured to assess the system's potential for drug delivery. Chapter 6 presents the conclusion, summarising the key findings of the thesis and discussing potential directions for future research based on the outcomes of this work.

Item Type	Thesis (PhD)
URI	https://centaur.reading.ac.uk/id/eprint/130832
Identification Number/DOI	10.48683/1926.00130832
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy
Date on Title Page	October 2024
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