PT  - JOURNAL ARTICLE
AU  - Hye Jung Lee
AU  - Gary Riley
AU  - Olufumni Johnson
AU  - Jeffrey L. Cleland
AU  - Norman Kim
AU  - Margarita Charnis
AU  - Leonie Bailey
AU  - Eileen Duenas
AU  - Azin Shahzamani
AU  - Melinda Marian
AU  - Andrew J. S. Jones
AU  - Scott D. Putney
TI  - <em>In Vivo</em> Characterization of Sustained-Release Formulations of Human Growth Hormone
DP  - 1997 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1431--1439
VI  - 281
IP  - 3
4099  - http://jpet.aspetjournals.org/content/281/3/1431.short
4100  - http://jpet.aspetjournals.org/content/281/3/1431.full
SO  - J Pharmacol Exp Ther1997 Jun 01; 281
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