Defense Date

2008

Document Type

Thesis

Degree Name

Master of Science

Department

Biomedical Engineering

First Advisor

Hu Yang

Abstract

This study describes a novel thermoresponsive dendritic polyethylene glycol-poly(D, L-lactide) (PEG-PDLLA) core-shell nanoparticle with potential for drug delivery and controlled release. A series of dendritic PEG-PDLLA nanoparticles were synthesized through conjugation of PEG to Starburst™ polyamidoamine (PAMAM) dendrimer G3.0 and subsequent ring-opening polymerization of DLLA, in which PEG chain length (i.e., MW=1500, 6000 or 12000 Dalton) was varied; however, the feeding molar ratio of DLLA monomers to the overall PEG repeat units on the dendrimer surface was kept at 1:1. Linear PEG-PDLLA copolymers were also syntheiszed under the same condition and used as control. According to our results, dendritic PEG-PDLLA in aqueous phase could self-assemble into spherical aggregates and the size of spherical aggregates increased with PEG chain length increase. Further, spherical aggregates made of dendritic PEG-PDLLA exhibited magnified temperature-dependence in terms of solubility change and dimension expansion as compared to linear PEG-PDLLA. The most significant size expansion was observed in particles made of dendritic PEG (12000)-PDLLA, which was twice as much as that of particles made of linear PEG (12000)-PDLLA. Water insoluble antitumor drug camptothecin (CPT) was used as a model drug for encapsulation and release studies. Spherical aggregates encapsulated more CPT when dendritic PEG-PDLLA had longer PEG-PDLLA chain and/or when temperature was elevated to body temperature. This study demonstrated that nanoscale clustering PEG-PDLLA through dendrimers magnified the thermo-sensitivity of PEG-PDLLA. Successful development of such a new particulate system made of dendritic PEG-PDLLA with an expandable dimension in response to temperature change generated a new direction for designing stimuli-responsive materials.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

December 2008

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