title: In vitro and in vivo evaluation of drug-eluting microspheres designed for transarterial chemoembolization therapy.
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.
authors.affiliation: Department of Biomedical Engineering/Biomaterials Science, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Daniël G M
authors.initials: DG
authors.lastname: Molin
authors.affiliation: Interfacultary Research Centre on Biomaterials (CEIB), University of Liège, Chemistry Institute B6C, B-4000 Liege (Sart-Tilman), Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Sevrin
authors.affiliation: Interfacultary Research Centre on Biomaterials (CEIB), University of Liège, Chemistry Institute B6C, B-4000 Liege (Sart-Tilman), Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Grandfils
authors.affiliation: Department of Physiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Nynke M S
authors.initials: NM
authors.lastname: van den Akker
authors.affiliation: Department of Physiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Mick
authors.initials: M
authors.lastname: Gagliardi
authors.affiliation: Faculty of Humanities and Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Menno L
authors.initials: ML
authors.lastname: Knetsch
authors.affiliation: Department of Biomedical Engineering/Biomaterials Science, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Tammo
authors.initials: T
authors.lastname: Delhaas
authors.affiliation: 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.
authors.forename: Leo H
authors.initials: LH
authors.lastname: Koole
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004621:Embolization, Therapeutic; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011091:Polyesters / Q000737:chemistry; D000077157:Sorafenib; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011091:Polyesters; D009536:Niacinamide; C033616:poly(lactide); D000077157:Sorafenib; D002945:Cisplatin
keywords: Biodegradation; Chemoembolization; Controlled local drug release; Poly(lactic acid) microspheres; Tumor growth inhibition