Preparation of Chitosan and Trimethylchitosan (TMC) Particles for Oral Vaccine Delivery

Name: Supavadee Boontha

keyword: Chitosan trimethylchitosan particles oral vaccine delivery

LCSH: Oral -- vaccines

Abstract: The principal aim of this thesis was to develop chitosan and trimethylchitosan (TMC) particles for oral Japanese encephalitis virus (JEV) delivery. In this study, three types of chitosan having different molecular weight (MW) and their respective TMC synthesized with a degree of quaternization (DQ) of 20%, 40% and 60% were used to prepare particles by ionic gelation method. The study started with preparation of chitosan and TMC particles having the potential for oral vaccine delivery using ovalbumin (OVA) as a model antigen. This step included the investigation of the effect of types of polymers (i.e. chitosan and TMC), the MW of chitosan and the DQ of TMC on the formation of particles and the characteristics of the particles obtained by optimizing the amount of tripolyphosphate (TPP) added. The chitosan and TMC particles prepared were tested for their potential to enhance immune response to OVA following oral immunization. Subsequently, the best formulations were selected and tested for the ability to induce immune response to JEV. The results showed that the amount of TPP added has an effect on the formation of chitosan and TMC particles. The formation of chitosan particles required higher amount of TPP than that of TMC particles. Using the same amount of TPP, the MW of chitosan did not have an effect on the formation of particles whereas the DQ of TMC did have. TMC particles with a DQ of 60% could not be prepared because of its high water solubility. Based on theirs high loading capacity of OVA and slow release profile, particles prepared using chitosan with low and medium MW and theirs respective TMC with a DQ of 40% which was shown to be the most potent in the parallel study via nasal route were selected to test for the ability to enhance immune response to OVA. Chitosan was likely to enhance higher immune responses than TMC. Thus, only chitosans with three different MWs were selected to test for the ability to initiate immune response to JEV. It was found that JEV encapsulated in all types of chitosan particles could induce the JEV-neutralizing antibodies levels higher than the minimal requested level (>1:10) by World Health Organization (WHO) following oral immunization in Swiss albino mice. However, the JEV-neutralizing antibodies initiated by particles prepared using three types of chitosan were not significantly different. In conclusion, the results of this thesis demonstrate that chitosan particles as adjuvant have the feasibility for oral JEV immunization and the MW of chitosan appeared to have no effect on the ability to elicite protective neutralizing antibodies to JEV in Swiss albino mice after oral immunization. Interestingly, although the differences were not statistically significant, free JEV (i.e. JEV in sterile water for injection (SWFI)) seemed to be better in the initiation of immune responses to JEV compared with particles-encapsulated JEV. Thus, the further work on the enhanced of immune initiation against JEV encapsulated in any delivery systems is necessary to be carefully considered.

NARESUAN UNIVERSITY. NARESUAN UNIVERSITY LIBRARY

Address: PHITSANULOK

Email: library@nu.ac.th

Name: Tasana Pitaksuteepong

Role: Advisor

Created: 2569

Modified: 2026-05-01

Issued: 2026-05-01

วิทยานิพนธ์/Thesis

application/pdf

eng

DegreeName: Doctor of Philosophy

Level: Doctoral Degree

Descipline: Pharmaceutical Sciences

Grantor: Naresuan University

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