Effect of PEGylation on stability of peptide in poly(lactide-co-glycolide) microspheres.
The purpose of this study was to evaluate the effect of PEGylation on the stabilization of peptide in poly(D,L-lactide-co-glycolide) (PLGA) microspheres for sustained release delivery. As model peptide, growth hormone-releasing peptide-6 (GHRP-6) was conjugated with succinimidyl propionate monomethoxy poly(ethylene glycol) (PEG) with an average molecular weight of 2000 Da. The mono-PEG-GHRP-6 was separated by ion-exchange chromatography, and its molecular mass was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The microspheres encapsulating native GHRP-6 or mono-PEG-GHRP-6 were prepared using the single oil-in-water emulsion solvent evaporation method. During incubation in a 0.1 M phosphate buffer (pH 7.4) for one month at 37 degrees C, native GHRP-6 microspheres were identified to form several acylated peptides by reversed-phase HPLC and MALDI-TOF MS, whereas the mono-PEG-GHRP-6 microspheres was not affected from peptide acylation by PLGA. This study demonstrates that PEGylation can stabilize peptide against the acylation reaction occurred in PLGA microspheres.
Park
Eun Ji
EJ
SungKyunKwan University, Suwon, Korea.
Tak
Tae Hyuk
TH
Na
Dong Hee
DH
Lee
Kang Choon
KC
D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011098:Polyglactin 910 / Q000737:chemistry* / Q000378:metabolism; D055550:Protein Stability; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D009842:Oligopeptides; D011098:Polyglactin 910; D011092:Polyethylene Glycols; C041048:growth hormone releasing hexapeptide