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

Wang Y 1 , Molin DG 2 , Sevrin C 3 , Grandfils C 3 , van den Akker NM 2 , Gagliardi M 2 Show all authors , Knetsch ML 4 , Delhaas T 1 , Koole LH 5

Affiliations 

  • 1 Department of Biomedical Engineering/Biomaterials Science, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
  • 2 Department of Physiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
  • 3 Interfacultary Research Centre on Biomaterials (CEIB), University of Liège, Chemistry Institute B6C, B-4000 Liege (Sart-Tilman), Belgium
  • 4 Faculty of Humanities and Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
  • 5 Department of Biomedical Engineering/Biomaterials Science, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands; INterface BIOmaterials B.V, Van Iterson Building (Chemelot Campus), Burgemeester Lemmensstraat 364, 6163 JT Geleen, The Netherlands; Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Jalan Universiti, 50603 Kuala Lumpur, Malaysia. Electronic address: koole.leo@gmail.com
Int J Pharm, 2016 Apr 30;503(1-2):150-62.
PMID: 26965198 DOI: 10.1016/j.ijpharm.2016.03.002

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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