Defense Date

2008

Document Type

Thesis

Degree Name

Master of Science

Department

Biomedical Engineering

First Advisor

Hu Yang

Abstract

In this study we describe novel polyionic dendrimer – PEG hydrogels for drug delivery. Hydrogels have a crosslinked insoluble network of polymer chains, which have found many applications including drug delivery and tissue regeneration. Dendrimers provide an ideal platform for drug delivery as they possess a well-defined highly branched nanoscale architecture with many reactive surface groups. Their highly clustered surface groups allow for targeted drug delivery and high drug payload to enhance therapeutic effectiveness. This study presented a new type of polyionic hydrogels based on dendrimers with potential applications in drug delivery and tissue engineering. Polyethylene glycol (PEG) with various chain lengths [1500, 6000 , 12000 Da] was first conjugated to the Starburst™ G3.0 PAMAM dendrimer to form stealth dendrimers through one ending site of PEG using p-nitro phenyl chloroformate and Triethylamine. The free hydroxyl group of PEG was further converted to an acrylate group using acrolyl chloride and Triethylamine. The conjugation was characterized with 1H-NMR. The Ninhydrin assay was used to estimate the loading degree of PEG on the dendrimer surface. The molecular weight and loading degree of PEG was varied. Hydrogel formation was realized by subjecting dendrimer-PEG acrylate to UV exposure for a brief period of time at the presence of Eosin Y, Triethanolamine [TEOA] and 1 vinyl 2 Pyrrolidinone [NVP] photo initiator system. Viscosity increase was observed after hydrogel formation. PEGylated G3.0 PAMAM dendrimer served as cross-linking agent to form hydrogels because of its multiple functionalities. PEGylated half generation dendrimer G3.5 was subjected to hydrogel formation and its swelling behavior was studied. Better hydrogel formation was observed with increased PEG arm length. The surface charges conferred by terminal groups on the dendrimer surface made the hydrogel polyionic with controllable charge density. This new type of hydrogel has many favorable biological properties such as non toxicity and non immunogenecity and multifunctional ties for a variety of in vivo applications. Current studies have demonstrated feasibility of chemistry and hydrogel formation. The swelling studies demonstrated pH sensitive behavior. Degradation of hydrogel was observed, for low PEGylated dendrimer degradation also demonstrated pH sensitivity. Controlled drug delivery and release were also investigated. Hydrophobic drug Cyclosprine A was used, we envision that hydrophobic dendrimer core will used for drug encapsulation and delivery, and later release in controlled fashion. The polymer and hydrogels were evaluated for in vitro cytotoxicity and cell internalization.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2008

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