TY - JOUR
T1 - Pharmacokinetic and efficacy study of cisplatin and paclitaxel formulated in a new injectable poly(sebacic-co-ricinoleic acid) polymer
AU - Levy-Nissenbaum, Etgar
AU - Khan, Wahid
AU - Pawar, Rajendra P.
AU - Tabakman, Rinat
AU - Naftali, Esmira
AU - Winkler, Ilan
AU - Kaufman, Olga
AU - Klapper, Leah
AU - Domb, Abraham J.
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Cisplatin
KW - Efficacy study
KW - Localized delivery system
KW - Paclitaxel
KW - Pharmacokinetics
KW - Poly(sebacic-co-ricinoleic acid)
UR - http://www.scopus.com/inward/record.url?scp=84866010251&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2012.06.004
DO - 10.1016/j.ejpb.2012.06.004
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C2 - 22732267
AN - SCOPUS:84866010251
SN - 0939-6411
VL - 82
SP - 85
EP - 93
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
IS - 1
ER -