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Dissertation
Synthesis, characterization, and application of biodegradable polymeric prodrug micelles for long-term drug delivery
Doctor of Philosophy (Ph.D.), Drexel University
Oct 2005
DOI:
https://doi.org/10.17918/etd-879
Abstract
Long-term drug delivery has several advantages such increasing bioavialability of drugs, reduction of pharmaceutical side effects, and increased patient compliance. Nanoparticles, such as block copolymer micelles, worm-like micelles, liposomes and polymersomes, have been proposed recently in the literature as promising drug delivery vehicles. Specifically, block copolymer micelles have advantages for drug delivery such as small size (< 100 nm) and hydrophilic outer shell that provides for increased in vivo halflife imparting a "stealth" nature to the particles. Drugs covalently attached to a polymer chain, known as prodrugs, can significantly enhance drug incorporation efficiency. Additionally, the drug release could be further controlled through the conjugate chemistry. In this work a biodegradable block copolymer prodrug was synthesized with the antipsychotic drug haloperidol. These polymeric prodrugs were formulated into nanoscale micelle-like structures, which were then characterized for size, morphology, stability, and drug loading capability. Micelles were found to be stable for use as a drug delivery vehicle, remaining intact upon dilution below the critical micelle concentration. In vitro release was evaluated from various formulations of micelles, and ranged from 3 to 5 days. Release from polymeric prodrug micelles most closely approached a linear release profile. Furthermore, in vivo behavioral studies were performed to assess haloperidol bioactivity from drug loaded micelles on ketamine induced hyperlocomotion. Results were consistent with in vitro release data, showing that conjugate and combination micelles continued to release drug 4 days post injection, attenuating the effects of the ketamine induced hyperlocomotion. Additionally, results indicate that the sedative side effects of haloperidol were reduced with the micelle delivery systems as compared to the acute haloperidol injection.
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Details
- Title
- Synthesis, characterization, and application of biodegradable polymeric prodrug micelles for long-term drug delivery
- Creators
- Meredith L. Hans - DU
- Contributors
- Anthony M. Lowman (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Chemical (and Biological) Engineering [Historical]; College of Engineering (1970-2026); Drexel University
- Other Identifier
- 879; 991014632156604721