title: Tailored delivery of active keratinocyte growth factor from biodegradable polymer formulations.
abstract: 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 mM, 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.
authors.affiliation: Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, New York 14260-3000, USA.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Cho
authors.forename: Zunyu
authors.initials: Z
authors.lastname: Tao
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Tehan
authors.forename: Frank V
authors.initials: FV
authors.lastname: Bright
authors.forename: Wesley L
authors.initials: WL
authors.lastname: Hicks
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gardella
authors.forename: Robert
authors.initials: R
authors.lastname: Hard
mesh_terms: D001672:Biocompatible Materials / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D007118:Immunoassay; D007700:Kinetics; D011108:Polymers / Q000378:metabolism*; D013057:Spectrum Analysis
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors