title: Acylation of peptides by lactic acid solutions.
abstract: To simplify the search for effective mechanisms to suppress peptide acylation inside drug delivery devices made of poly(D,L-lactic acid) (PLA) and poly(lactic-co-glycolic acid), we were looking for a suitable model system that would allow screening of strategies for peptide stabilization. With their low pH and the presence of lactic acid oligomers, diluted lactic acid solutions promised to be a suitable test system that mimics the microclimate in degrading PLA devices. We created solutions of 1-50% (w/w) lactic acid by dilution of concentrated lactic acid. Using high performance liquid chromatography (HPLC) and high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis, oligomer hydrolysis was monitored during the equilibration process of the diluted solutions. Their final oligomer content was determined by titration and by calculations based on HPLC data. HPLC-MS analysis of human atrial natriuretic peptide (ANP) stability in different lactic acid solutions at 37 degrees C for 4 weeks demonstrated that ANP underwent acylation even in diluted solutions containing only 0.05% (w/w) lactic acid oligomers. Purity analysis of lactic acid solutions allowed us to compare the conditions in the solution test-system to the microclimate that prevails inside degrading PLA microspheres.
authors.affiliation: Department of Pharmaceutical Technology, University of Regensburg, Regensburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lucke
authors.forename: Achim
authors.initials: A
authors.lastname: Göpferich
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D009320:Atrial Natriuretic Factor / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D006016:Glycolates / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D019344:Lactic Acid / Q000737:chemistry*; D013058:Mass Spectrometry; D008863:Microspheres; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D006016:Glycolates; D010455:Peptides; D014677:Pharmaceutical Vehicles; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D009320:Atrial Natriuretic Factor