title: LDI-glycerol polyurethane implants exhibit controlled release of DB-67 and anti-tumor activity in vitro against malignant gliomas.
abstract: The purpose of the present study was to develop a biodegradable and biocompatible polyurethane drug delivery system based on lysine diisocyanate (LDI) and glycerol for the controlled release of 7-tert-butyldimethylsilyl-10-hydroxy-camptothecin (DB-67). DB-67 has yet to be implemented in any clinical therapies due to the inability to delivered it in sufficient quantities to impact tumor growth and disease progression. To remedy this, DB-67 was covalently incorporated into our delivery system by way of an organometallic urethane catalyst and was found to be dispersed evenly throughout the LDI-glycerol polyurethane discs. Scanning electron micrographs indicate that the LDI-glycerol discs are uniform and possess a pore distribution typical of the non-solvent casting technique used to prepare them. The release rates of DB-67 from the LDI-glycerol discs were found to vary with both time and temperature and were shown capable of delivering therapeutic concentrations of DB-67 in vitro. Cellular proliferation assays demonstrate that empty LDI-glycerol discs alone do not significantly alter the growth of malignant human glioma cell lines (U87, T98G, LN229 and SG388). DB-67-loaded LDI-glycerol polyurethane discs were found to inhibit cellular proliferation by 50% on average in all the malignant glioma cell lines tested. These results clearly demonstrate the long-term, slow release of DB-67 from LDI-glycerol polyurethane discs and their potential for postoperative intracranial chemotherapy of cancers.
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: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000473:pathology*; D005990:Glycerol / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D017953:Isocyanates / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D017646:Organosilicon Compounds / Q000737:chemistry / Q000494:pharmacology*; D011140:Polyurethanes / Q000378:metabolism*; D019736:Prostheses and Implants; D012996:Solutions; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D017953:Isocyanates; D017646:Organosilicon Compounds; D011140:Polyurethanes; D012996:Solutions; D013607:Tablets; C511489:lysine diisocyanate; C415575:7-tert-butyldimethylsilyl-10-hydroxycamptothecin; D008239:Lysine; D005990:Glycerol; D002166:Camptothecin