Date of Award

5-1-2013

Degree Type

Dissertation

University or Center

Clark Atlanta University(CAU)

School

School of Arts and Sciences

Degree Name

Ph.D.

Chemistry

First Advisor

Ishrat M. Khan, Ph.D

Second Advisor

James Bu, Ph.D

Third Advisor

Cass D. Parker, Ph.D

Abstract

Functionalized nano materials have an expansive range of potential uses in bio medical applications. Functionalized synthetic (biocompatible and/or biodegradable) polymers that control or monitor cell signaling can be effective antagonists and promising drug candidates. We have developed a series of biodegradable functional polymer systems (with dimensions in the nanoscale) for creating allergy-effective drugs, using RBL mast cells and anti-2,4 dinitrophenyl (DNP) IgE antibodies that sensitize these cells by binding to high affinity IgE receptors(FceRI); creating polymers which are effective inhibitors of degranulation of mast cells stimulated by a potent allergen. The inhibition is possible because of the specific interaction of the functional polymers with the proteins (IgE) on the mast cell surfaces to control cell-signaling i.e. intelligent design of functional materials to manipulate cellular functions. The functional polymer system is based on biodegradable poly(lactides) carrying two, three or four 2,4-dinitrophenyl (DNP) groups. Although these DNP-functionalized ligands do not stimulate the granule exocytosis response, they have the potential to inhibit the robust response stimulated by other multivalent DNP ligands. These polymeric ligands are effective inhibitors of degranulation of mast cells stimulated by a potent allergen and thus are a potential model drug system. Additionally these lactide based polymers bind and achieve steady state binding with solution IgE within a few seconds at low concentrations; achieving about 75% of the binding below 0.2 uM. The preparation, characterization, processing and effectiveness of the functional polymers to control material-cell interactions will be discussed

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Notice to Users, Transmittal and Statement of Understanding

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