Pharmacokinetic and efficacy study of cisplatin and paclitaxel formulated in a new injectable poly(sebacic-co-ricinoleic acid) polymer.
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.
BioLineRx Ltd., Jerusalem, Israel.
Etgar
E
Levy-Nissenbaum
Wahid
W
Khan
Rajendra P
RP
Pawar
Rinat
R
Tabakman
Esmira
E
Naftali
Ilan
I
Winkler
Olga
O
Kaufman
Leah
L
Klapper
Abraham J
AJ
Domb
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002945:Cisplatin / Q000008:administration & dosage; D003652:Decanoic Acids / Q000737:chemistry*; D003692:Delayed-Action Preparations; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000008:administration & dosage; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D012277:Ricinoleic Acids / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
D003652:Decanoic Acids; D003692:Delayed-Action Preparations; C493322:Poly(sebacic acid-co-ricinoleic acid); D011108:Polymers; D012277:Ricinoleic Acids; D017239:Paclitaxel; D002945:Cisplatin