Date of Award

2010

Degree Type

Thesis

Degree Name

Master of Engineering Science

Program

Chemical and Biochemical Engineering

Supervisor

Dr. Jin Zhang

Second Advisor

Dr. Jesse Zhu

Abstract

Controlled drug delivery technology represents one of the frontier areas of science, which involves a multidisciplinary scientific approach and contributes to human health care. Hydrogel based nanoparticles (NPs) have gained considerable attention in recent years as one of the most promising nanoparticulate drug delivery systems, owing to their unique potentials by combining the characteristics of a hydrogel system, i.e. hydrophilicity and extremely high water content, with a nanoparticle i.e. very small size. In this research, hydrogel-based nanoparticles, i.e. gelatin NPs, were used as a carrier to encapsulate protein drug for controlled release in a prolonged manner. Bovine serum albumin (BSA) as a model protein drug was loaded within gelatin NPs through an in situ two-step disolvation method. The average diameter of the NPs was 180±10 nm and the average pore size was 2.82 nm. The releasing kinetics of BSA from gelatin NPs in phosphate buffer saline (PBS) was studied through monitoring of BSA concentration by UV-Vis spectrometry over 6 days. The effects of crosslinking and pH values on the release profiles were also investigated. The experimental results indicated that the rate of BSA release from gelatin NPs decreased with increasing concentrations of the cross-linker. Furthermore, the drug releasing study also clearly showed that the acidic condition enabled prolonging the release profile. In addition, another pH sensitive hydrogel, chitosan, along with gelatin has been chosen to make a more stable hydrogel nanocomposite system. A solution casting method was developed to synthesize BSA loaded gelatin NPs grafted on chitosan. Based on different drying methods, two different types of gelatin-chitosan nanocomposites were prepared, one was a dense nanocomposite and the second was a porous nanocomposite. The thickness of the biopolymer patch was about 160 μm. The release profile of BSA from the two types of hydrogel nanocomposites was studied through UV-Vis spectrophotometry. The results revealed that BSA was released from the porous nanocomposite over 10 days and from the dense nanocomposite over 16 days. Furthermore, swelling behavior, pH sensitivity, degradation rate, percentage of elongation, young’s modulus were all studied for the analysis of biological and mechanical properties of the nanocomposites. All of these studies showed that the chitosan-gelatin hydrogels are a potential carrier of water-soluble protein drugs. Moreover, the hydrogel nanocomposite further prolonged the drug releasing over the single gelatin nanoparticulate system. It is expected that this new biodegradable polymer nanocomposite can be alternative materials of implant medical device for protein therapy.

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