Date of Award

2018

Document Type

Open Access Master's Thesis

Degree Name

Master of Science in Biomedical Engineering (MS)

Administrative Home Department

Department of Biomedical Engineering

Advisor 1

Megan C. Frost

Committee Member 1

Smitha Rao

Committee Member 2

Lanrong Bi

Abstract

After injury, wound healing is a complex sequential cascade of events essential for the proper recovery of the wound without the scar formation. Nitric oxide (NO) is a small, endogenous free-radical gas with antimicrobial, vasodilating and growth factor stimulating properties. NO has wide biomedical application especially in wound healing however, its usability is hindered due its administration problem as it is highly unstable.

In this work, poly (l-lactic acid) microparticles encapsulated with NO donor S-nitroso-N-acetyl-D-penicillamine (SNAP) were prepared using water-in-oil-water double emulsion solvent evaporation method for controlled delivery for NO at the specific site. The NO release from SNAP-PLLA microparticles prepared at two different stirring speeds (500 and 2500 RPM) was evaluated using three main SNAP decomposition triggers i.e. light, copper and ascorbic acid. The light controlled on and off mechanism of nitric oxide release from the microparticles at different intensities was demonstrated that can be used to control the amount of NO release depending on the need. An average total NO release of 6.11 ± 1.71 x10-08 for 9 hrs. and 8.43 ± 2.92 x10-08 for 13 hrs. was observed from microparticle(500) andmicroparticle(2500) respectively on exposure to light, copper (II) and ascorbate. Furthermore, these SNAP-PLLA microparticles were embedded into thermosensitive chitosan-agarose hydrogel to form microparticle-hydrogel composite. These composites have demonstrated NO release on exposure to light. An ascorbic acid chitosan-agarose hydrogel composite system was also used to evaluate the NO release in the presence of only ascorbic acid from the microparticle hydrogel composite. A significant difference in average total NO release from both microparticles as well as microparticle-hydrogel composite was observed because of varying size parameter. These findings suggest that these microparticle as well as microparticle-hydrogel composite formulations may be useful for wound site administration of nitric oxide to accelerate wound healing process delayed due to dysfunction in endogenous NO production caused by pathological infection.

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