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Drug release from pH-responsive thermogelling pentablock copolymers.

Determan MD, Cox JP, Mallapragada SK

Department of Chemical and Biological Engineering, Iowa State University and Ames Laboratory,144 Spedding Hall, Ames, Iowa 50011, USA.

A novel pH-dependent injectable sustained delivery system was developed by utilizing a cationic pentablock copolymer that exhibits a thermoreversible sol-gel transition. Aqueous solutions of the pentablock copolymer, consisting of poly(2-diethylaminoethyl-methyl methacrylate)-poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-poly(2-diethylaminoethyl-methyl methacrylate) (PDEAEM(25)-PEO(100)-PPO(65)-PEO(100)-PDEAEM(25)) exhibit temperature and pH dependent micellization due to the lower critical solution temperature of the PPO blocks and the polyelectrolyte character of the PDEAEM blocks, respectively. Aqueous solutions of the copolymers above 12 wt % are free flowing liquids at room temperature and form elastic physical hydrogels reversibly above 37 degrees C. Hydrophobic probe absorbance studies indicate that pentablock copolymer micelles increase the solubility of sparingly soluble drugs. Solutions of the pentablock copolymer that form gels at body temperature exhibit sustained zero-order release in in vitro experiments. The release rates of model drugs and proteins were significantly influenced by the pH of the release media, thereby making these polymers ideal candidates for modulated drug delivery.

Published 1 June 2007 in J Biomed Mater Res A, 81(2): 326-33.
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