In vitro and in vivo evaluation of drug-eluting microspheres designed for transarterial chemoembolization therapy

Yujing Wang, Daniel G. M. Molin, Chantal Sevrin, Christian Grandfils, Nynke M. S. van den Akker, Mick Gagliardi, Menno L. Knetsch, Tammo Delhaas, Levinus Koole*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Pages (from-to)150-162
JournalInternational Journal of Pharmaceutics
Volume503
Issue number1-2
DOIs
Publication statusPublished - 30 Apr 2016

Keywords

  • Poly(lactic acid) microspheres
  • Controlled local drug release
  • Tumor growth inhibition
  • Chemoembolization
  • Biodegradation

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