Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 409, Issue 1-2, Pages 185-193Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2011.02.058
Keywords
Doxorubicin; Ion exchange; Bioresorbable; Hydrogel microspheres
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Non-bioresorbable drug eluting microspheres are being increasingly used for the treatment of unresectable liver tumors, whereas bioresorbable microspheres have not received much attention. In this study, bioresorbable microspheres prepared from chitosan and carboxymethyl cellulose were loaded with doxorubicin (Doxo) via ion-exchange interactions with carboxylic groups in the microspheres. With a 25-40% decrease in the microsphere size depending on their size ranges, the microspheres could load a maximum of 0.3-0.7 mg Doxo/mg dry spheres. As confirmed by confocal microscopy, Doxo was mainly concentrated in the outer 20 +/- 5 mu m surface layer of the microspheres. The loaded microspheres were stable in aqueous dispersions without aggregation for a prolonged period of time but degradable in a lysozyme solution. Furthermore, the loaded microspheres exhibited a noticeable pH-sensitive behavior with accelerated release of Doxo in acidic environment due to the protonation of carboxylic groups in the microspheres. Compared to commercial non-resorbable drug eluting beads, the loaded bioresorbable microspheres showed a sustained release manner in phosphate buffered saline (PBS). The release data were fitted to an empirical relationship, which reveals a non-Fickian transport mechanism (n = 0.55-0.59). These results demonstrate that the bioresorbable microspheres are promising as attractive carriers for Doxo. (C) 2011 Elsevier B.V. All rights reserved.
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