Date of Graduation

5-2015

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Zaharoff, David A.

Abstract

Chitosan-based nanoparticles are under investigation as delivery vehicles for drugs, genes, and proteins. Due to the biocompatibility, mucoadhesive nature, and biodegradable nature of chitosan and binding qualities, anionic nature, and biocompatible qualities of heparin, chitosan/heparin nanoparticles (CHNPs) are a promising platform for the delivery of labile proteins. However, the literature lacks a definitive process to control the size, efficiency, and yield of CHNPs at higher concentrations of reagents. Additionally there is a need to improve loading efficiency of CHNPs. In this study CHNPs have been synthesized and characterized for size, yield, protein loading efficiency, and release. The CHNPs were prepared through ionotropic gelation of chitosan with heparin. Chitosan concentration (.5mg/ml, 1mg/ml and 2mg/ml), amount of heparin added (0.004mg, 0.010mg, 0.016mg, 0.080mg, and 0.160mg), and number of sonications (0, 1, 2, 3, and 4) are influential factors in determining particle size, yield, and loading efficiency. The optimized loaded particles had an average size of 740nm, loading efficiency of 99% using Bovine serum albumin-fluorescein isothiocyanate conjugate (FITC-BSA) and 40% using Interleukin-12 (IL-12), and average mass yield of 9mg of nanoparticles. This study provides important methodology to control size, yield, and loading efficiency of chitosan/heparin nanoparticles. These particles, because they can be loaded in mild aqueous conditions, represent a promising delivery platform for cytokines and other labile proteins. Our future studies will determine if CHNPs loaded with the anti-tumor cytokine IL-12 is capable of controlling established tumors.

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