title: Effect of PEGylation on stability of peptide in poly(lactide-co-glycolide) microspheres.
abstract: 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.
authors.affiliation: SungKyunKwan University, Suwon, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Park
authors.forename: Tae Hyuk
authors.initials: TH
authors.lastname: Tak
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Na
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
mesh_terms: 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
chemical_list: D009842:Oligopeptides; D011098:Polyglactin 910; D011092:Polyethylene Glycols; C041048:growth hormone releasing hexapeptide