Acylation of peptides by lactic acid solutions

Lucke, Andrea and Goepferich, Achim (2003) Acylation of peptides by lactic acid solutions. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 55 (1). pp. 27-33. ISSN 0939-6411

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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 37degreesC 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. (C) 2002 Elsevier Science B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: CONTROLLED-RELEASE; STABILIZATION; MICROSPHERES; lactic acid; oligomers; atrial natriuretic peptide; stability; acylation
Subjects: 600 Technology > 615 Pharmacy
Divisions: Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Sep 2021 07:02
Last Modified: 22 Sep 2021 07:02
URI: https://pred.uni-regensburg.de/id/eprint/39443

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