Formation of acylated growth hormone-releasing peptide-6 by poly(lactide-co-glycolide) and its biological activity.
The purpose of this study was to investigate the formation of acylated impurity resulting from a chemical reaction between the growth hormone-releasing peptide-6 (GHRP-6) and poly(lactide-co-glycolide) (PLGA) and the effect of peptide acylation on the in vivo biological activity of GHRP-6. The peptide acylation pattern of GHRP-6 by hydrophilic PLGA polymers with different molecular weights was characterized by reversed-phase high-performance liquid chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Higher levels of acylated GHRP-6 were produced with the higher molecular weight PLGA, which might be due to the slower degradation rate of the polymer. The evaluation of the biological activity in rats showed that the acylated GHRP-6 had a much lower activity than the intact GHRP-6. This finding suggests that the acylation reaction would decrease the effectiveness of the GHRP-6 formulation such as PLGA microspheres. Therefore, a strategy for stabilizing the GHRP-6 will be necessary for the development of a successful formulation of PLGA microspheres.
Na
Dong Hee
DH
College of Pharmacy, Kyungsung University, Busan, Korea.
Lee
Jeong Eun
JE
Jang
Sun Woo
SW
Lee
Kang Choon
KC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D013006:Growth Hormone / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D009842:Oligopeptides; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone