Lucke, Andrea and Kiermaier, Josef and Goepferich, Achim (2002) Peptide acylation by poly(alpha-hydroxy esters). PHARMACEUTICAL RESEARCH, 19 (2): UNSP 0724-. pp. 175-181. ISSN 0724-8741
Full text not available from this repository. (Request a copy)Abstract
Purpose. Poly(lactic acid) (PLA) and poly (lactic-co-glycolic acid) (PLGA) microsphercs were investigated concerning the possible acylation of incorporated peptides. Methods. Atrial natriuretic peptide (ANP) and salmon calcitonin (sCT) were encapsulated into PLA and PLGA microspheres. Peptide integrity was monitored by HPLC-MS analysis during microsphere degradation for four weeks. sCT fragmentation with endoproteinase Glu-C was used for identifying modified amino acids. Peptide stability in lactic acid solutions was investigated to elucidate possible mechanisms for preventing peptide acylation. Results. Both peptides were acylated by lactic and glycolic acid units inside degrading microspheres in a time-dependent manner. After 21 days, 60% ANP and 7% sCT inside PLA microspheres were acylated. Fragmentation of sCT with endoproteinase Glu-C revealed that besides the N-terminal amine group, lysine, tyrosine or serine are further possible targets to acylation. Stability studies of the peptides in lactic acid solutions suggest that oligomers are the major acylation source and that lower oligomer concentration and higher pH substantially decreased the reaction velocity. Conclusions. The use of PLA and PLGA for drug delivery needs substantially more circumspection. As, according to FDA standards, the potential hazards of peptide acylation products need to be assessed, our findings may have significant implications for products already on the market. Techniques to minimize the acylation reaction are suggested.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR DELIVERY; PLGA MICROSPHERES; SUSTAINED-RELEASE; DRUG-DELIVERY; PROTEIN; biodegradable polymer; poly(lactic acid); poly(lactic-co-glycolic acid); peptide stability; acylation |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) Chemistry and Pharmacy > Central Analytical Services |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Nov 2021 07:37 |
| Last Modified: | 15 Nov 2021 07:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40651 |
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