title: Simultaneous drug release at different rates from biodegradable polyurethane foams.
abstract: In this study, we present an approach for the simultaneous release of multiple drug compounds at different rates from single-phase polyurethane foams constructed from lysine diisocyanate (LDI) and glycerol. The anti-cancer compounds DB-67 and doxorubicin were covalently incorporated into polyurethane foams, whereby drug release can then occur in concert with material degradation. To begin, the reactions of DB-67 and doxorubicin with LDI in the presence of a tertiary amine catalyst were monitored with infrared spectroscopy; each compound formed urethane linkages with LDI. Fluorescent spectra of DB-67 and doxorubicin were then recorded in phosphate-buffered saline, pH 7.4 (PBS), to ensure that each anti-cancer compound could be quantitatively detected alone and in combination. Doxorubicin and DB-67 were then incorporated into a series of degradable LDI-glycerol polyurethane foams alone and in combination with one another. The sol content, average porosity and drug distribution throughout each foam sample was measured and found to be similar amongst all foam samples. The stability of DB-67 and doxorubicin's fluorescent signal was then assessed over a 2-week period at 70 degrees C. Release rates of the compounds from the foams were assessed over a 10-week period at 4, 22, 37 and 70 degrees C by way of fluorescence spectroscopy. Release was found to be temperature-dependent, with rates related to the chemical structure of the incorporated drug. This study demonstrates that differential release of covalently bound drugs is possible from simple single-phase, degradable polyurethane foams.
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: Jianying
authors.initials: J
authors.lastname: Zhang
authors.forename: Stephané
authors.initials: S
authors.lastname: Petoud
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Beckman
mesh_terms: D020341:Absorbable Implants; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D005740:Gases / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry*; D017953:Isocyanates / Q000737:chemistry*; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry; D008422:Materials Testing; D017646:Organosilicon Compounds / Q000008:administration & dosage / Q000737:chemistry; D011140:Polyurethanes / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D005740:Gases; D017953:Isocyanates; D017646:Organosilicon Compounds; D011140:Polyurethanes; C511489:lysine diisocyanate; C415575:7-tert-butyldimethylsilyl-10-hydroxycamptothecin; D004317:Doxorubicin; D008239:Lysine; D005990:Glycerol; D002166:Camptothecin