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

Abstract

Recombinant human transforming growth factor beta1 (TGF-beta1) 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 microg/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-beta1 was 83.4 +/- 13.1 and 54.2 +/- 12.1% for PEG contents of 0 and 5%, respectively. The FITC-BSA and TGF-beta1 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 microg (based on 1 mg microparticles) of loaded FITC-BSA and 3.4 +/- 0.2 and 2.2 +/- 0.3 ng of loaded TGF-beta1 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 microg of FITC-BSA and 2.0 +/- 0.2 ng of TGF-beta1 were released in pH 7.4 buffer after 28 days, while only 1.7 +/- 0.3 microg 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.

Controlled release of bioactive TGF-β1 from microspheres embedded within biodegradable hydrogels

“…TGF-b 1 was encapsulated into PLGA microspheres using a double emulsion technique, following a protocol previously described [31]. Briefly, 250 mg PLGA was dissolved in 2 mL of MC.…”

Controlled release of proteins from pluronic-based nano-carrier

“…Instead, the solubility of protein seems to be a key factor, as previously reported. [19][20][21] Proteins with a high water solubility (BSA, Lysozyme) showed much faster release than growth factors with a low solubility. Between VEGF and BMP-2, VEGF with a relatively higher solubility than BMP-2 showed a significantly faster release than BMP-2 in spite of the higher molecular weight.…”

Current concepts and applications in the musculoskeletal and peripheral nervous systems

“…18 Moreover, recent studies indicate that the initial mechanical properties can be improved by directing cell migration and differentiation within the material with the use of growth factors (TGF-b1). 19 As periosteum has osteogenic potency through the release of periosteum-derived osteoblasts, it can be used to generate bone. Periosteum grafts have been successfully applied to induce new bone formation, with vascularized periosteum showing a constant or even increasing level of osteogenic capacity over time.…”