Cj. Goodwin et al., RELEASE OF BIOACTIVE HUMAN GROWTH-HORMONE FROM A BIODEGRADABLE MATERIAL - POLY(EPSILON-CAPROLACTONE), Journal of biomedical materials research, 40(2), 1998, pp. 204-213
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.