期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 503, 期 1-2, 页码 150-162出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2016.03.002
关键词
Poly(lactic acid) microspheres; Controlled local drug release; Tumor growth inhibition; Chemoembolization; Biodegradation
资金
- EU (through Interreg IVa)
- government of the Province Dutch Limburg
- Dutch National Ministry of Economic Affairs, Agriculture & Innovation, Maastricht University
- Limburg Bank for Industry Innovation (LIOF)
Poly(D,L-lactic acid) biodegradable microspheres, loaded with the drugs cisplatin and/or sorafenib tosylate, were prepared, characterized and studied. Degradation of the microspheres, and release of cisplatin and/or sorafenib tosylate from them, were investigated in detail. Incubation of the drug-carrying microspheres in phosphate buffered saline (pH = 7.4) revealed slow degradation. Nevertheless, significant release of cisplatin and sorafenib tosylate from microspheres loaded with both drugs was apparent in vitro; this can be attributed to their porous structure. Supernatants from microspheres loaded with both drugs showed strong toxic effects on cells (i.e. endothelial cells, fibroblast cells and Renca tumor cells) and potent anti-angiogenic effect in the matrigel endothelial tube assay. In vivo anti-tumor effects of the microspheres were also observed, in a Renca tumor mouse model. The poly(D,L-lactic acid) microspheres containing both cisplatin and sorafenib tosylate revealed highest therapeutic efficacy, probably demonstrating that combined local administration of cisplatin and sorafenib tosylate synergistically inhibits tumor growth in situ. In conclusion, this study demonstrates the applicability of biodegradable poly(D,L-lactic acid) microspheres loaded with cisplatin and sorafenib tosylate for local drug delivery as well as the potential of these microspheres for future use in transarterial chemoembolization. (C) 2016 Elsevier B.V. All rights reserved.
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