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Intracellular degradation of microspheres based on cross-linked dextran hydrogels or amphiphilic block copolymers: A comparative Raman microscopy study

Authors Henk-Jan van Manen, Aart A van Apeldoorn, Ruud Verrijk, Clemens A van Blitterswijk, Cees Otto

Published 15 July 2007 Volume 2007:2(2) Pages 241—252

Henk-Jan van Manen1, Aart A van Apeldoorn2, Ruud Verrijk3, Clemens A van Blitterswijk2, Cees Otto1

1Biophysical Engineering Group, Institute for Biomedical Technology (BMTI), and MESA+ Institute for Nanotechnology, University of Twente, The Netherlands; 2Polymer Chemistry and Biomaterials Group, Institute for Biomedical Technology (BMTI), University of Twente, The Netherlands; 3OctoPlus, Zernikedreef 12, The Netherlands

Abstract: Micro- and nanospheres composed of biodegradable polymers show promise as versatile devices for the controlled delivery of biopharmaceuticals. Whereas important properties such as drug release profiles, biocompatibility, and (bio)degradability have been determined for many types of biodegradable particles, information about particle degradation inside phagocytic cells is usually lacking. Here, we report the use of confocal Raman microscopy to obtain chemical information about cross-linked dextran hydrogel microspheres and amphiphilic poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) microspheres inside RAW 264.7 macrophage phagosomes. Using quantitative Raman microspectroscopy, we show that the dextran concentration inside phagocytosed dextran microspheres decreases with cell incubation time. In contrast to dextran microspheres, we did not observe PEGT/PBT microsphere degradation after 1 week of internalization by macrophages, confirming previous studies showing that dextran microsphere degradation proceeds faster than PEGT/PBT degradation. Raman microscopy further showed the conversion of macrophages to lipid-laden foam cells upon prolonged incubation with both types of microspheres, suggesting that a cellular inflammatory response is induced by these biomaterials in cell culture. Our results exemplify the power of Raman microscopy to characterize microsphere degradation in cells and offer exciting prospects for this technique as a noninvasive, label-free optical tool in biomaterials histology and tissue engineering.

Keywords: biodegradation, microspheres, Raman microscopy, phagocytosis, drug delivery

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