LDI–glycerol polyurethane implants exhibit controlled release of DB-67 and anti-tumor activity in vitro against malignant gliomas

Abstract : The purpose of the present study was to develop a biodegradable and biocompatible polyurethane drug delivery system based on lysine diisocyanate (LDI) and glycerol for the controlled release of 7-tert-butyldimethylsilyl-10-hydroxy-camptothecin (DB-67). DB-67 has yet to be implemented in any clinical therapies due to the inability to delivered it in sufficient quantities to impact tumor growth and disease progression. To remedy this, DB-67 was covalently incorporated into our delivery system by way of an organometallic urethane catalyst and was found to be dispersed evenly throughout the LDI-glycerol polyurethane discs. Scanning electron micrographs indicate that the LDI-glycerol discs are uniform and possess a pore distribution typical of the non-solvent casting technique used to prepare them. The release rates of DB-67 from the LDI-glycerol discs were found to vary with both time and temperature and were shown capable of delivering therapeutic concentrations of DB-67 in vitro. Cellular proliferation assays demonstrate that empty LDI-glycerol discs alone do not significantly alter the growth of malignant human glioma cell lines (U87, T98G, LN229 and SG388). DB-67-loaded LDI-glycerol polyurethane discs were found to inhibit cellular proliferation by 50% on average in all the malignant glioma cell lines tested. These results clearly demonstrate the long-term, slow release of DB-67 from LDI-glycerol polyurethane discs and their potential for postoperative intracranial chemotherapy of cancers.
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https://hal.archives-ouvertes.fr/hal-02090839
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Submitted on : Friday, April 5, 2019 - 11:07:08 AM
Last modification on : Friday, April 5, 2019 - 3:19:26 PM

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Wesley Sivak, Ian Pollack, Stephane Petoud, William Zamboni, Jianying Zhang, et al.. LDI–glycerol polyurethane implants exhibit controlled release of DB-67 and anti-tumor activity in vitro against malignant gliomas. Acta Biomaterialia, Elsevier, 2008, 4 (4), pp.852-862. ⟨10.1016/j.actbio.2007.10.012⟩. ⟨hal-02090839⟩

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