Graduation Date

Summer 8-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Pharmacology and Experimental Neuroscience

First Advisor

Howard E. Gendelman

Second Advisor

Bhavesh D. Kevadiya

Abstract

Polymeric porous particles are designed, prepared, and deployed for co-delivery of therapeutics, tissue engineering and regenerative medicine. In pharmaceutical sciences, particle shape, size, surface topography and porosity control cargo loading and material tuning. Herein, we characterized six branched aliphatic hydrocarbon-based porogens, formulated to create pores in multilayer microspheres. This was done to develop a simplified delivery platform through single emulsion solvent evaporation techniques. The effects of the porogens on various biocompatible polymers, that included polycaprolactone, poly(lactic-co-glycolic acid) and polylactic acid, were tested by state-of-art solid state characterizations, along with the evaluation of biodegradation and cargo release parameters of the porous MS. The porous multilayer microsphere can be further developed for effective drug delivery and immunization strategies.

Moreover, sustained drug delivery and release of therapeutic proteins has played key roles in pharmaceutical product development(s). This is based on known improvements in duration of drug action, reduced toxicities, and regimen compliance. For vaccinations, slow-controlled delivery and sustained antigen release can elicit lasting immunity. Such outcomes can obviate the needs for repeated dose immunizations. To build on these prior successes we developed multipolymer biodegradable microspheres (MS) to facilitate antigen loading and release of a chemical inactivated SARS-CoV-2 virus. A single emulsion solvent evaporation method was developed for the MS that was followed by extensive physicochemical, microscopic, and spectral characterizations. Proof of concept immunizations of the MS loaded SARS CoV-2 antigens demonstrated humoral and cellular immune antiviral responses serving in support of further formulation developments.

Comments

2022 Copyright, the authors

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