Release of bioactive human growth hormone from a biodegradable material: poly(epsilon-caprolactone)

We have characterized the biodegradable material poly(epsilon-caprolactone) (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 particulate leaching; the latter yielded porous PCL discs. The degree of porosity, which was assessed by scanning electron microscopy, could be controlled by incorporating selected concentrations of particulate sodium chloride during the manufacturing process. Bioactive hGH released from the PCL preparations was quantified with a highly sensitive and precise bioassay which was based upon hGH activation of rat lymphoma Nb2 cells. Eluates obtained from control discs of PCL which had not been loaded with hGH proved to be nontoxic when tested on these cells. The release of bioactive hGH from hormone-loaded nonporous discs of PCL was found to be a direct function of the initial hormone loading dose. Increased porosity of the discs manufactured by solvent casting particulate leaching increased the delivery of hGH from discs which had been immersion loaded. However, hGH release after surface loading was independent of porosity. Hormone concentrations were also assessed by immunoassay so that the ratios of bio- to immunoactivity (B:I ratio) of the hormone 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 the mild incorporation procedures utilized had not adversely affected the 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 bioactive site.