Year of Award
2023
Document Type
Thesis
Degree Type
Master of Science (MS)
Degree Name
Pharmaceutical Sciences
Department or School/College
BMED
Committee Chair
Walid Abdelwahab
Committee Co-chair
David Burkhart
Commitee Members
Shannon Miller, Kevan Roberts
Publisher
University of Montana
Subject Categories
Pharmaceutics and Drug Design
Abstract
Intranasal vaccines hold enormous potential for improving vaccine efficacy against respiratory pathogens by activating the mucosal immune system. The urgency for novel approaches in vaccine development is amplified by the recent COVID-19 pandemic. Most intranasal vaccines that were developed are either live-attenuated or inactivated vaccine candidates that demonstrated poor safety profiles. Protein-based subunit vaccines represent a safe and cost-effective alternative, but they are often weak immunogenically. TLR7/8 adjuvants such as INI-4001 have shown promise for enhancing the humoral and cellular immunogenicity of protein-based subunit vaccines. It is theorized that poor immunogenicity of intranasal protein subunit vaccines is due to low bioavailability attributed to the mucosal barrier and mucociliary clearance. Vaccine delivery systems that adhere to the mucosa and temporarily stop mucociliary clearance have shown improved vaccine delivery to mucosal associated lymphoid tissue. In this work, we aim to improve mucoadhesion of INI-4001 loaded liposomes by the addition of diverse mucoadhesive excipients. This research also aims to develop reliable analytical tools to model and assess the mucoadhesive capacity of nanoparticle-based intranasal vaccine formulations. Each chosen excipient was formulated with INI-4001 loaded liposomes of various charge and screened for acceptable formulation characteristics. Stable formulations were then evaluated for mucoadhesive properties by measuring mucin-particle interactions using dynamic light scattering (DLS). Mucoadhesive liposomes were also evaluated by a flow through assay using ex vivo porcine tracheal tissue. Cationic liposomes formulated with TMC and DSPE-PEG2000-maleimide emerged as lead mucoadhesive formulations based on these in vitro and ex vivo experiments. These formulations and their respective controls will be evaluated for immunogenicity in a murine influenza in vivo study to correlate mucosal retention with immunogenicity of intranasal vaccines.
Recommended Citation
Lorentz, Elizabeth Brander, "MODIFIED TLR7/8 ADJUVANTED LIPOSOMES FOR IMPROVED INTRANASAL DELIVERY OF SUBUNIT VACCINES" (2023). Graduate Student Theses, Dissertations, & Professional Papers. 12255.
https://scholarworks.umt.edu/etd/12255
© Copyright 2023 Elizabeth Brander Lorentz