title: 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 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.
authors.affiliation: Department of Bioengineering, School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Wesley N
authors.initials: WN
authors.lastname: Sivak
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Stéphane
authors.initials: S
authors.lastname: Petoud
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Beckman
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002166:Camptothecin / Q000008:administration & dosage / Q000737:chemistry*; D002384:Catalysis; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods*; D005740:Gases / Q000737:chemistry; D017953:Isocyanates / Q000737:chemistry*; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry; D008422:Materials Testing; D011140:Polyurethanes / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005740:Gases; D017953:Isocyanates; D011140:Polyurethanes; C511489:lysine diisocyanate; D008239:Lysine; D002166:Camptothecin