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.