Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-28T04:46:48.185Z Has data issue: false hasContentIssue false

The influence of pH on the molecular degradation mechanism of PLGA

Published online by Cambridge University Press:  30 October 2018

Rainhard Machatschek
Affiliation:
Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht and Berlin-Brandenburg Center for Regenerative Therapies, Kantstraße 55, 14513 Teltow, Germany
Burkhard Schulz
Affiliation:
Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht and Berlin-Brandenburg Center for Regenerative Therapies, Kantstraße 55, 14513 Teltow, Germany Institute of Chemistry, University of Potsdam, Karl-Liebknecht-Straße 24-25,14469 Potsdam, Germany
Andreas Lendlein*
Affiliation:
Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht and Berlin-Brandenburg Center for Regenerative Therapies, Kantstraße 55, 14513 Teltow, Germany Institute of Chemistry, University of Potsdam, Karl-Liebknecht-Straße 24-25,14469 Potsdam, Germany
*
*Correspondence to: Andreas Lendlein, Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstraße 55, 14513 Teltow, Germany. E-Mail: andreas.lendlein@hzg.de
Get access

Abstract

Poly[(rac-lactide)-co-glycolide] (PLGA) is used in medicine to provide mechanical support for healing tissue or as matrix for controlled drug release. The properties of this copolymer depend on the evolution of the molecular weight of the material during degradation, which is determined by the kinetics of the cleavage of hydrolysable bonds. The generally accepted description of the degradation of PLGA is a random fragmentation that is autocatalyzed by the accumulation of acidic fragments inside the bulk material. Since mechanistic studies with lactide oligomers have concluded a chain-end scission mechanism and monolayer degradation experiments with polylactide found no accelerated degradation at lower pH, we hypothesize that the impact of acidic fragments on the molecular degradation kinetics of PLGA is overestimated. By means of the Langmuir monolayer degradation technique, the molecular degradation kinetics of PLGA at different pH could be determined. Protons did not catalyze the degradation of PLGA. The molecular mechanism at neutral pH and low pH is a combination of random and chainend-cut events, while the degradation under strongly alkaline conditions is determined by rapid chainend cuts. We suggest that the degradation of bulk PLGA is not catalyzed by the acidic degradation products. Instead, increased concentration of small fragments leads to accelerated mass loss via fast chain-end cut events. In the future, we aim to substantiate the proposed molecular degradation mechanism of PLGA with interfacial rheology.

Type
Articles
Copyright
Copyright © Materials Research Society 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ma, X., Oyamada, S., Wu, T., Robich, M. P., Wu, H., Wang, X., Buchholz, B., McCarthy, S., Bianchi, C. F., Sellke, F. W. and Laham, R., Journal of Biomedical Materials Research Part A 96A (4), 632638 (2011).CrossRefGoogle Scholar
Mathew, S., Baudis, S., Neffe, A. T., Behl, M., Wischke, C. and Lendlein, A., European Journal of Pharmaceutics and Biopharmaceutics 95, 1826 (2015).CrossRefGoogle Scholar
Zhu, X. and Braatz, R. D., Journal of Biomedical Materials Research Part A 103 (7), 22692279 (2015).CrossRefGoogle Scholar
Laycock, B., Nikolić, M., Colwell, J. M., Gauthier, E., Halley, P., Bottle, S. and George, G., Progress in Polymer Science 71 (Supplement C), 144189 (2017).CrossRefGoogle Scholar
van Nostrum, C. F., Veldhuis, T. F. J., Bos, G. W. and Hennink, W. E., Polymer 45 (20), 67796787 (2004).CrossRefGoogle Scholar
Kulkarni, A., Reiche, J. and Lendlein, A., Surface and Interface Analysis 39 (9), 740746 (2007).CrossRefGoogle Scholar
de Jong, S. J., Arias, E. R., Rijkers, D. T. S., van Nostrum, C. F., Kettenes-van den Bosch, J. J. and Hennink, W. E., Polymer 42 (7), 27952802 (2001).CrossRefGoogle Scholar
Hamoudi-Ben Yelles, M. C., Tran Tan, V., Danede, F., Willart, J. F. and Siepmann, J., Journal of Controlled Release 253, 1929 (2017).CrossRefGoogle Scholar
Siepmann, J., Elkharraz, K., Siepmann, F. and Klose, D., Biomacromolecules 6 (4), 23122319 (2005).CrossRefGoogle Scholar
Schone, A. C., Roch, T., Schulz, B. and Lendlein, A., J R Soc Interface 14 (130) (2017).CrossRefGoogle Scholar
Kim, H. C., Lee, H., Jung, H., Choi, Y. H., Meron, M., Lin, B., Bang, J. and Won, Y.-Y., Soft Matter 11 (28), 56665677 (2015).CrossRefGoogle Scholar
Li, J., Nemes, P. and Guo, J., Journal of Biomedical Materials Research Part B: Applied Biomaterials 106 (3), 11291137 (2018).CrossRefGoogle Scholar