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Pharmacokinetic and efficacy study of cisplatin and paclitaxel formulated in a new injectable poly(sebacic-co-ricinoleic acid) polymer.

Abstract
Injectable biodegradable polymer poly(sebacic-co-ricinoleic acid), P(SA-RA) is currently under development for intratumoral (IT) delivery of drugs for treating solid tumors. This study presents formulation development, pharmacokinetic and efficacy studies of two anticancer drugs (cisplatin and paclitaxel) formulated with P(SA-RA) polymer. In pharmacokinetic study, systemic exposure and pharmacokinetic parameters of cisplatin/paclitaxel following single intravenous (IV) or subcutaneous (SC) doses of cisplatin/paclitaxel was compared with intramuscular (IM) or SC doses of cisplatin/paclitaxel formulated with P(SA-RA) polymer in male CD rat. Simultaneously, the tumor reduction effect and toxicity for these formulations were evaluated in human FaDu head and neck tumor xenograft subcutaneous nude mouse model. Pharmacokinetic data reflect the lower maximal concentrations and sustained release of polymer-cisplatin/paclitaxel formulations compared to standard cisplatin/paclitaxel administration. Regarding efficacy study, a single IT or near the tumor injection (NT) of polymer-paclitaxel or polymer-cisplatin formulation significantly reduced the tumor size, compared to the standard paclitaxel or cisplatin treatments. No death or toxicity and no effect on body weight as well as macroscopic and/or microscopic changes in or near the injected area were observed, proving biocompatibility and acceptability of polymer-formulations. In conclusion, the developed formulation demonstrated controlled release and significant efficacy in delivering these agents and exhibit potential for further clinical development.
AuthorsEtgar Levy-Nissenbaum, Wahid Khan, Rajendra P Pawar, Rinat Tabakman, Esmira Naftali, Ilan Winkler, Olga Kaufman, Leah Klapper, Abraham J Domb
JournalEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 82 Issue 1 Pg. 85-93 (Sep 2012) ISSN: 1873-3441 [Electronic] Netherlands
PMID22732267 (Publication Type: Comparative Study, Journal Article)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Decanoic Acids
  • Delayed-Action Preparations
  • Poly(sebacic acid-co-ricinoleic acid)
  • Polymers
  • Ricinoleic Acids
  • Paclitaxel
  • Cisplatin
Topics
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, pharmacokinetics, pharmacology)
  • Cisplatin (administration & dosage)
  • Decanoic Acids (chemistry)
  • Delayed-Action Preparations
  • Head and Neck Neoplasms (drug therapy, pathology)
  • Humans
  • Injections, Intramuscular
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Nude
  • Paclitaxel (administration & dosage)
  • Polymers (chemistry)
  • Rats
  • Ricinoleic Acids (chemistry)
  • Xenograft Model Antitumor Assays

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