Catalyst-dependent drug loading of LDI–glycerol polyurethane foams leads to differing controlled release profiles

Abstract

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 11 week 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 < 1.0 × 10 −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.