RELEASE OF BIOACTIVE HUMAN GROWTH-HORMONE FROM A BIODEGRADABLE MATERIAL - POLY(EPSILON-CAPROLACTONE)

We have characterized the biodegradable material poly(epsilon-caprolac tone) (PCL) as a delivery system for recombinant human growth hormone (hGH). Two contrasting methods for the manufacture of the biomaterial were investigated: namely, solvent casting and solvent casting particu late leaching; the latter yielded porous PCL discs. The degree of poro sity, which was assessed by scanning electron microscopy, could be con trolled by incorporating selected concentrations of particulate sodium chloride during the manufacturing process. Bioactive hGH released fro m the PCL preparations was quantified with a highly sensitive and prec ise bioassay which was based upon hGH activation of rat lymphoma Nb2 c ells. Eluates obtained from control discs of PCL which had not been lo aded with hGH proved to be nontoxic when tested on these cells. The re lease of bioactive hGH from hormone-loaded nonporous discs of PCL was found to be a direct function of the initial hormone loading dose. Inc reased porosity of the discs manufactured by solvent casting particula te leaching increased the delivery of hGH from discs which had been im mersion loaded. However, hGH release after surface loading was indepen dent of porosity. Hormone concentrations were also assessed by immunoa ssay so that the ratios of bio-to immunoactivity (B:I ratio) of the ho rmone release could be determined. We found that the B:I ratio of the hormone after release from unstored discs was identical to that of the hormone prior to its incorporation into the PCL, demonstrating that t he mild incorporation procedures utilized had not adversely affected t he structural integrity of the hormone. However, if the hormone-loaded discs were stored at 37 degrees C prior to elution, the B:I ratios of the hGH released decreased indicating that this compromised the bioac tive site. (C) 1998 John Wiley & Sons, Inc.