RT Journal Article SR Electronic T1 In Vivo Characterization of Sustained-Release Formulations of Human Growth Hormone JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1431 OP 1439 VO 281 IS 3 A1 Lee, Hye Jung A1 Riley, Gary A1 Johnson, Olufumni A1 Cleland, Jeffrey L. A1 Kim, Norman A1 Charnis, Margarita A1 Bailey, Leonie A1 Duenas, Eileen A1 Shahzamani, Azin A1 Marian, Melinda A1 Jones, Andrew J. S. A1 Putney, Scott D. YR 1997 UL http://jpet.aspetjournals.org/content/281/3/1431.abstract AB Long-acting formulations of recombinant human growth hormone (rhGH) were prepared by stabilizing and encapsulating the protein into three different injectable, biodegradable microsphere formulations composed of polymers of lactic and glycolic acid. The formulations were compared in juvenile rhesus monkeys by measuring the serum levels of rhGH and two proteins induced by hGH, insulin-like growth factor-I and IGF binding protein-3 (IGFBP-3) after single s.c. administration. All three formulations, which differed principally in the composition of the polymer, provided sustained elevated levels of all three proteins for several weeks, and the rate of release of rhGH differed among the formulations consistent with the molecular weight of the polymer used. All three formulations induced a higher level of insulin-like growth factor-I and insulin-like growth factor binding protein than was induced by daily injections of the same amount of rhGH in solution. After three monthly injections of one of the formulations, both the rhGH and IGF-I levels remained elevated for nearly 90 days. Immunogenicity of the rhGH released from this formulation, as assessed by the incidence of seroconversion to hGH and the titer of anti-hGH antibody in both the rhesus monkeys and transgenic mice expressing rhGH, was no greater than that of the unencapsulated protein. In addition, the microsphere injection sites appeared normal by macroscopic evaluation between 1 to 2 mo after microsphere administration and by microscopic evaluation between 2 to 3 mo. These results show that serum levels of a therapeutic protein can be sustained for an extended period when encapsulated into different formulations of injectable, biodegradable microspheres. The American Society for Pharmacology and Experimental Therapeutics