Journal
JOURNAL OF CONTROLLED RELEASE
Volume 92, Issue 1-2, Pages 39-48Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0168-3659(03)00294-3
Keywords
biodegradable polymer; polyphosphate; controlled drug delivery; protein encapsulation; hydrophilicity
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Many biodegradable polymers have been developed for controlled drug delivery. The plethora of drug therapies and types of drugs demand different formulations, fabrications conditions and release kinetics. No one single polymer can satisfy all the requirements. To extend the properties of poly(D,L-lactide) (PLA), we synthesized copolymers of PLA and poly(ethylethylene phosphate) (PEEP) by ring-opening polymerization using Al(O(i)pr)(3) as the initiator. The copolymers were structurally characterized by IR and H-1 NMR. DSC data confirmed the formation of random microphase structure in all the copolymers, and showed a decrease of T-g from 43.2 to -22.6 degreesC when the molar content of ethylethylene phosphate (EEP) increased from 5 to 40%. The hydrophilicity of the copolymers increased with EEP content. In contrast to the degradation behavior of PLA, disc samples made of PLAEEP90 showed a linear weight loss profile in PBS (pH 7.4) at 37 degreesC. BSA microspheres using PLAEEP90 were prepared by double-emulsion method, yielding a loading level of 4.3% and a loading efficiency of 75%. The BSA release profile consisted of an initial burst (9%) on the first day, followed by a daily 4% release for the following 40 days, resulting in 91% of the BSA release in a near linear manner. The released BSA remained intact according to SDS-PAGE data. Cytotoxicity and histopathology studies showed low toxicity in HeLa cells and good tissue biocompatibility in mouse brain, respectively. PLAEEP is a promising biodegradable polymer for controlled drug delivery. (C) 2003 Elsevier B.V. All rights reserved.
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