Controlled release of transforming growth factor ?1 from biodegradable polymer microparticles

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Abstract
Recombinant human transforming growth factor β1 (TGF-β1) was incorporated into biodegradable microparticles of blends of poly(dl-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) at 6 ng/1 mg microparticles. Fluorescein isothiocynate labeled bovine serum albumin (FITC-BSA) was coencapsulated as a porogen at 4 μg/1 mg of microparticles. The effects of PEG content (0, 1, or 5 wt %) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for up to 28 days. The entrapment yield of TGF-β1 was 83.4 ± 13.1 and 54.2 ± 12.1% for PEG contents of 0 and 5%, respectively. The FITC-BSA and TGF-β1 were both released in a multiphasic fashion including an initial burst effect. Increasing the PEG content resulted in the decreased cumulative mass of released proteins. By day 28, 3.8 ± 0.1 and 2.8 ± 0.3 μg (based on 1 mg microparticles) of loaded FITC-BSA and 3.4 ± 0.2 and 2.2 ± 0.3 ng of loaded TGF-β1 were released into pH 7.4 phosphate buffered saline (PBS) from microparticles with 0 and 5% PEG, respectively. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. For microparticles with 5% PEG, 2.3 ± 0.1 μg of FITC-BSA and 2.0 ± 0.2 ng of TGF-β1 were released in pH 7.4 buffer after 28 days, while only 1.7 ± 0.3 μg and 1.3 ± 0.4 ng of the corresponding proteins were released in pH 3 buffer. The degradation of PLGA was also enhanced at 5% PEG content, which was significantly accelerated at acidic pH conditions. The calculated half-lives of PLGA were 20.3 ± 0.9 and 15.9 ± 1.2 days for PEG contents of 0 and 5%, respectively, in pH 7.4 PBS and 14.8 ± 0.4 and 5.5 ± 0.1 days for 5% PEG in pH 7.4 and 3 buffers, respectively. These results suggest that PLGA/PEG blend microparticles are useful as delivery vehicles for controlled release of growth factors. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 50, 440–451, 2000.