Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1558 | Acta Biomaterialia | 2008 | 12 Pages |
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.