Date of Completion

4-30-2013

Embargo Period

4-24-2014

Keywords

hydrogel/microsphere composite coating, implantable biosensor, drug delivery

Major Advisor

Diane J. Burgess

Associate Advisor

Fotios Papadimitrakopoulos

Associate Advisor

Bodhisattwa Chaudhuri

Field of Study

Pharmaceutical Science

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

A novel composite system consisting of poly(lactic-co-glycolic) acid (PLGA) microsphere dispersed in poly(vinyl alcohol) (PVA) hydrogels has been developed as a “smart” drug eluting biocompatible coating for implantable biosensors. The objective of this research was to characterize and optimize this composite coating together with both dummy and functional glucose sensors to: 1) prevent the foreign body response (FBR) to the implanted biosensors; 2) ensure sufficient glucose transport to the sensing elements; 3) understand factors contributing to the negative tissue reaction (initial trauma, and implant size); and 4) ensure adequate in vitro stability of the composites.

PLGA microsphere/PVA hydrogel composite coatings together with dummy sensors (the same dimension as glucose sensors) were evaluated in both normal and diabetic rats. It was determined that the diabetic condition altered the acute inflammatory phase. Local delivery of dexamethasone successfully prevented inflammation and fibrous encapsulation at the implant sites. The feasibility of utilizing PLGA microsphere/PVA hydrogel composites as coatings for implantable biosensors was demonstrated.

The glucose diffusivity of the composite coatings as well as their effect on the basic characteristics of the biosensors was evaluated. The composite coatings did not affect sensor functionality. The microsphere loading and degradation affected the glucose diffusivity of the composites, and consequently affected sensor sensitivity. Microsphere degradation increased glucose diffusivity through the composite coatings over time, which resulted in a gradual increase in the sensor sensitivity. This increase in porosity as a result of microsphere degradation could be a useful strategy to compensate the progressive sensitivity loss due to biofouling.

The effect of initial trauma and implant size on the FBR was investigated. The extent of the acute inflammation was mainly controlled by the level of the initial trauma, whereas the development of fibrous encapsulation was mainly affected by the implant size.

The in vitro stability of the composite coatings under various conditions was determined. Physical aging occurred in the microspheres at ambient temperature, whilst the moisture caused plasticization and induced hydrolytic degradation of the PLGA polymer. Accordingly, refrigeration conditions are recommended to ensure storage stability of the composite coatings.

In conclusion, utilization of the PLGA microsphere/PVA hydrogel composites as biocompatible coatings for implantable biosensors is a promising strategy to enhance their in vivo performance.

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