Biodegradable triblock copolymer microspheres for drug delivery based on thermosensitive property of triblock copolymer

Update item information
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Kwon, Young Min
Title Biodegradable triblock copolymer microspheres for drug delivery based on thermosensitive property of triblock copolymer
Date 2003-12
Description Extensive research has recently been focused on injectable polymeric drug delivery system for the delivery of bioactive agents such as anticancer agents, proteins, or DNA in the form of drug-loaded particulate systems (i.e., microspheres and nanoparticles) for the last decade. Conventional protein-loaded microsphere preparation involves use of water-immiscible organic solvent such as methylene chloride under harsh condition and the resultant microsphere typically exhibits initial burst effect followed by incomplete release of protein drug. An experiment was designed to monitor insulin aggregation induced by water/methylene chloride interface by a turbidimetric method. Insulin at the interface quickly underwent aggregation. This paved the way for a novel approach to prepare biodegradable microspheres without using organic solvent by utilizing unique aqueous sol-gel transition property of triblock copolymer poly(lactic-co-glycolic acid) (PLGA)-PEG-PLGA. A comparative study was carried out using microspheres of the same polymer and drug but prepared by different methods: Msp A (water-based microsphere) and Msp B (w/o/w). Insulin release was carried out in vitro and Msp A showed continuous release over 2 weeks while Msp B exhibited an initial burst effect followed by no release. Circular dichroism (CD) spectroscopy of released insulin demonstrated that insulin from Msp A maintained secondary structure integrity while that from Msp B did not. Confocal microcopy of FITC-labeled insulin showed that fluorescence was homogeneous in Msp A but not homogeneous in Msp B. In an in vivo study using streptozotocin-induced diabetic rats, Msp B exhibited an initial burst release as shown by hypoglycemic shock while Msp A showed less burst and prolonged release for 10 days. The versatility of this triblock copolymer led to the design of an aqueous-based nanoparticle carrier for paclitaxel. Drug-loaded nanoparticle demonstrated control of cultured vascular smooth muscle cell proliferation for potential treatment of restenosis. The unique property of thermosensitive, biodegradable triblock copolymer made it possible to design novel methods of preparing organic solvent-free particulate systems for the delivery of protein and water-insoluble drug.
Type Text
Publisher University of Utah
Subject Block Copolymers; Drugs
Subject MESH Polymers; Pharmacology; Drug Delivery Systems; Pharmaceutical Preparations
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Biodegradable triblock copolymer microspheres for drug delivery based on thermosensitive property of triblock copolymer." Spencer S. Eccles Health Sciences Library. Print version of "Biodegradable triblock copolymer microspheres for drug delivery based on thermosensitive property of triblock copolymer." available at J. Willard Marriott Library Special Collection. RS43.5 2003 .K86
Rights Management © Young Min Kwon.
Format Medium application/pdf
Format Extent 2,148,562 bytes
Identifier undthes,5129
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship NIH GM 56908 and Macromed, Incorported, Sandy Utah and Higuchi Fellowship Award.
Master File Extent 2,148,637 bytes
ARK ark:/87278/s6w37z36
Setname ir_etd
Date Created 2012-04-24
Date Modified 2012-04-24
ID 190871
Reference URL https://collections.lib.utah.edu/ark:/87278/s6w37z36