Date of Award

5-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Pharmaceutical Sciences

Research Advisor

James R. Johnson, PhD.

Committee

Hassan Almoazen, PhD. Elizabeth A. Fitzpatrick, PhD. Timothy D. Mandrell, DVM, DACLAM. Richard J. Webby, PhD.

Abstract

Pulsatile release formulations for single dose vaccines have been studied for many years because of the advantages that they may provide to vaccine administration with a single dose instead of prime and booster shots.

The aim of this work is to develop novel formulations based on an In Situ Implant (ISI) systems to provide a modified vaccine release and altered immune response, which could act as a booster administration. This type of system was selected because ISI systems are used for long acting administration of various drugs and ease of administration. A typical ISI system is comprised of hydrophilic organic solvent (e.g. N-Methyl-2-Pyrrolidone, NMP) and hydrophobic polymer (e.g. poly (lactide-co-glycolide), PLGA). We have given this concept the name of AdjuGel to distinguish it from simple drug administration. It was developed by incorporating an oil (e.g. Acetyl Tributyl Citrate, ATBC) into an ISI system. When loaded with dissolved or suspended antigens, AdjuGel can be injected by syringe into the body. After injection, AdjuGel will solidify due to the dissipation of hydrophilic solvent and form an in situ semi-solid implant, which can hold oil and antigen for a delayed release.

It was found that an AdjuGel system, composed of ethyl acetate, ATBC and a hydrophobic polymer, such as PLGA or PLA, could stimulate delayed immune response. The delayed period for immune response was adjustable, which was determined by the degradation rates of polymers. A slower polymer degradation rate provided a longer delayed period for immune response.

DOI

10.21007/etd.cghs.2014.0376

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