Co-delivery of cisplatin and doxorubicin from calcium phosphate beads/matrix scaffolds for osteosarcoma therapy.

Ulrike Hess, Shakiba Shahabi, Laura Treccani, Philipp Streckbein, Christian Heiss, Kurosch Rezwan

Journal: Materials science & engineering. C, Materials for biological applications 2018;77():427-435

PMID: 28532049

Full Text on Elsevier Science View on PubMed

Abstract

Bone substitute materials with a controlled drug release ability can fill cavities caused by the resection of bone tumours and thereby combat any leftover bone cancer cells. The combined release of different cytostatics seems to enhance their toxicity. In this study, calcium phosphate beads and matrix scaffolds are combined for a long-term co-delivery of cis-diamminedichloroplatinum (cisplatin, CDDP) and doxorubicin hydrochloride (DOX) as clinical relevant model drugs. Tricalcium phosphate/alginate beads as additional drug carrier are produced by droplet extrusion with ionotropic gelation and incorporated in scaffold matrix by freeze gelation without sintering. CDDP shows a short burst release while DOX has a continuous release measurable over the entire study period of 40days. Drug release from matrix is decreased by ~30% compared to release from beads. Nevertheless, all formulations follow the Korsmeyer-Peppas release kinetic model and show Fickian diffusion. Cytotoxic activity was conducted on MG-63 osteosarcoma cells after 1, 4, and 7days with WST-1 cell viability assay. Co-loaded composites enhance activity towards MG-63 cells up to ~75% toxicity while reducing the released drug quantity. The results suggest that co-loaded beads/matrix scaffolds are highly promising for osteosarcoma therapy due to synergistic effects over a long period of more than a month.

Address: Advanced Ceramics, University of Bremen, Am Biologischen Garten 2, 28359 Bremen, Germany. Electronic address: [email protected].; Advanced Ceramics, University of Bremen, Am Biologischen Garten 2, 28359 Bremen, Germany. Electronic address: [email protected].; Advanced Ceramics, University of Bremen, Am Biologischen Garten 2, 28359 Bremen, Germany. Electronic address: [email protected].; Department for Cranio-Maxillofacial and Plastic Surgery, University Hospital of Giessen-Marburg GmbH, Campus Giessen, Klinikstrasse 33, 35392 Giessen, Germany; Laboratory of Experimental Surgery, Justus-Liebig-University of Giessen, Kerkrader Strasse 9, 35394 Giessen, Germany. Electronic address: [email protected].; Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg GmbH, Campus Giessen, Rudolf-Buchheim-Strasse 7, 35392 Giessen, Germany; Laboratory of Experimental Surgery, Justus-Liebig-University of Giessen, Kerkrader Strasse 9, 35394 Giessen, Germany. Electronic address: [email protected].; Advanced Ceramics, University of Bremen, Am Biologischen Garten 2, 28359 Bremen, Germany; MAPEX Center for Materials and Processes, University of Bremen, Am Fallturm 1, 28359 Bremen, Germany. Electronic address: [email protected].

DOI: 10.1016/j.msec.2017.03.164

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MeSH Terms: Bone Neoplasms, Calcium Phosphates, Cisplatin, Doxorubicin, Humans, Osteosarcoma