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.