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Tailored delivery of active keratinocyte growth factor from biodegradable polymer formulations
Author(s) -
Cho Eun Jeong,
Tao Zunyu,
Tang Ying,
Tehan Elizabeth C.,
Bright Frank V.,
Hicks Wesley L.,
Gardella Joseph A.,
Hard Robert
Publication year - 2003
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.10598
Subject(s) - materials science , polymer , glycolic acid , biodegradable polymer , biodegradation , pulmonary surfactant , solvent , keratinocyte growth factor , chromatography , chemical engineering , lactic acid , organic chemistry , composite material , growth factor , chemistry , biochemistry , receptor , biology , bacteria , engineering , genetics
We report the results of a high throughput screening campaign that is aimed to develop a biodegradable polymer‐based formulation to deliver active keratinocyte growth factor (KGF) and provide a means to tune the KGF delivery rate. A statistical design strategy was used to prepare and screen a series of polymer blends that were composed of poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and the surfactant sodium bis(ethylhexyl)sulfosuccinate (Aerosol‐OT, AOT). Chloroform was the solvent. Our high throughput screening method used a two‐tiered assessment strategy. At Level 1, we identified “lead” KFG‐loaded formulations that exhibited KGF emission spectra that were the most similar to the native KGF spectrum recorded in buffer. At Level 2, we used steady‐state emission and a homogeneous polarization immunoassay strategy to determine the concentration of total and active KGF, respectively, liberated from the lead formulations during biodegradation. After preparing and screening 2500 formulations, we identified several viable, lead formulations. An analysis of the data showed that the combination of PLA, PGA, and AOT were important to yield a high fraction of active KGF upon release from the formulation; no combination of any two together produced an effect as good as the ternary formulation. The optimum formulations that yielded the highest fraction of active KGF upon release had the following general features: PLA/PGA (w/w) near unity, AOT loading of 100–200 m M , water/AOT mole ratio of 10–20, and a pH between 6 and 8. PLA alone cast from chloroform delivered KGF, but that KGF did not bind to anti‐KGF antibodies (i.e., it was inactive). We can tune the KGF release kinetics by more than two orders of magnitude while maintaining the KGF activity upon liberation from the formulation by adjusting the PLA molecular weight. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 417–424, 2003