Controlled release of transforming growth factor β1 from biodegradable polymer microparticles

Lichun Lu, Georgios N. Stamatas, Antonios G. Mikos

Research output: Contribution to journalArticle

149 Citations (Scopus)

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 F1TC-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. (C) 2000 John Wiley and Sons, Inc.

Original languageEnglish (US)
Pages (from-to)440-451
Number of pages12
JournalJournal of Biomedical Materials Research
Volume50
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Biodegradable polymers
Transforming Growth Factors
Polyethylene glycols
Buffers
Proteins
glycolic acid
Phosphates
polylactic acid-polyglycolic acid copolymer
Intercellular Signaling Peptides and Proteins
Degradation
Agglomeration
Bovine Serum Albumin
Fluorescein

Keywords

  • Biodegradable microparticles
  • Bone regeneration
  • Growth factor delivery
  • Poly(DL-lactic-co-glycolic acid)
  • Poly(ethylene glycol)
  • Polymer blends
  • Transforming growth factor β1

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

Cite this

Controlled release of transforming growth factor β1 from biodegradable polymer microparticles. / Lu, Lichun; Stamatas, Georgios N.; Mikos, Antonios G.

In: Journal of Biomedical Materials Research, Vol. 50, No. 3, 2000, p. 440-451.

Research output: Contribution to journalArticle

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KW - Bone regeneration

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