The purpose of the present study was to develop biodegradable and biocompatible
polyurethane foams based on
lysine diisocyanate (LDI) and
glycerol to be used as drug-delivery systems for the controlled release of 7-tert-butyldimethylsilyl-10-hydroxy-camptothecin (DB-67). The impact of
urethane catalysts on cellular proliferation was assessed in an attempt to enhance the biocompatibility of our
polyurethane materials.
DB-67, a potent
camptothecin analog, was then incorporated into
LDI-glycerol polyurethane foams with two different
amine urethane catalysts: 1,4-diazobicyclo[2.2.2]-
octane (
DABCO) and 4,4'-(oxydi-2,1-ethane-diyl)bismorpholine (DMDEE). The material morphologies of the
polyurethane foams were analyzed via scanning electron microscopy, and
DB-67 distribution was assessed by way of fluorescence microscopy. Both foam morphology and
drug distribution were found to correlate to the
amine catalyst used. Hydrolytic release rates of
DB-67 from the
polyurethane foams were catalyst dependent and also demonstrated greater
drug loads being released at higher temperatures. The foams were capable of delivering therapeutic concentrations of
DB-67 in vitro over an 11week test period. Cellular proliferation assays demonstrate that empty LDI-
glycerol foams did not significantly alter the growth of malignant human
glioma cell lines (P<0.05).
DB-67 loaded
LDI-glycerol polyurethane foams were found to inhibit cellular proliferation by at least 75% in all the
malignant glioma cell lines tested (P<1.0x10(-8)). These results clearly demonstrate the long-term, catalyst-dependent release of
DB-67 from
LDI-glycerol polyurethane foams, indicating their potential for use in implantable
drug-delivery devices.