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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.
AuthorsWesley N Sivak, Ian F Pollack, Stéphane Petoud, William C Zamboni, Jianying Zhang, Eric J Beckman
JournalActa biomaterialia (Acta Biomater) Vol. 4 Issue 4 Pg. 852-62 (Jul 2008) ISSN: 1742-7061 [Print] England
PMID18440882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Delayed-Action Preparations
  • Isocyanates
  • Organosilicon Compounds
  • Polyurethanes
  • Solutions
  • Tablets
  • lysine diisocyanate
  • 7-tert-butyldimethylsilyl-10-hydroxycamptothecin
  • Lysine
  • Glycerol
  • Camptothecin
Topics
  • Camptothecin (analogs & derivatives, chemistry, pharmacology)
  • Cell Death (drug effects)
  • Cell Line, Tumor
  • Delayed-Action Preparations
  • Drug Screening Assays, Antitumor
  • Glioma (pathology)
  • Glycerol (chemistry, metabolism)
  • Humans
  • Isocyanates (chemistry, metabolism)
  • Lysine (analogs & derivatives, chemistry, metabolism)
  • Microscopy, Electron, Scanning
  • Organosilicon Compounds (chemistry, pharmacology)
  • Polyurethanes (metabolism)
  • Prostheses and Implants
  • Solutions
  • Spectrometry, Fluorescence
  • Spectroscopy, Fourier Transform Infrared
  • Tablets

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