DOI
https://doi.org/10.25772/PW92-K974
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