Biodistribution and efficacy of the anticancer drug, oxaliplatin palmitate acetate, in mice

Nikhil Biswas, Aiman Abu Ammar, Marina Frušić-Zlotkin, Naama Adi-Hen, Yonat Lehman-Katabi, Yael Levi-Kalisman, Taher Nassar, Simon Benita*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Oxaliplatin palmitate acetate (OPA), a platinum (IV) oxaliplatin derivative, was previously designed with the aim to improve the platinum-based anti-cancer therapy. In this work, we further explore the potential of OPA in extensive in vitro and in vivo studies. OPA in pancreatic (BxPC3-luc), lung (NCI-H1993) and liver (Hep3B) cancer cell lines showed a higher toxicity in comparison to oxaliplatin. The in vitro release kinetic experiments of OPA from the nanoparticles (NPs) under sink conditions exhibited a very rapid profile. Furthermore, OPA cannot be considered a prodrug of oxaliplatin, based on the OPA intact molecule pharmacokinetic profile study in rats. The formation of oxaliplatin from the biodegradation of OPA ranges only from 5% to 7% and both drugs were rapidly eliminated from the plasma. Pharmacokinetics of OPA PLGA nanoparticles in mice showed that nanoparticles failed to prolong the release of OPA in the plasma and did not add any therapeutic benefit over OPA solution, as suggested by the rapid in vitro release of OPA from nanoparticles. In pancreatic xenograft BxPC3-luc cancer model, both OPA in solution and OPA nanoparticles inhibited the tumor growth, equally and significantly, as compared to oxaliplatin. In liver xenograft Hep3B cancer model, OPA solution and cisplatin demonstrated good and similar antitumor efficacy. In lung xenograft NCI-H1993 cancer model, OPA solution, with a significant antitumor efficacy, was superior to cisplatin, which did not differ from the vehicle. In conclusion, OPA may offer a promising advance in platinum-based chemotherapy against various forms of cancers in an adequate dose and schedule.

Original languageAmerican English
Article number120740
Pages (from-to)1-11
JournalInternational Journal of Pharmaceutics
Volume604
DOIs
StatePublished - 15 Jul 2021

Bibliographical note

Funding Information:
This research was supported by a grant from Israel Innovation Authority to BioNanoSim (BNS) and Prof. Simon Benita (IIA grant number #65753).

Funding Information:
This research was supported by a grant from Israel Innovation Authority to BioNanoSim (BNS) and Prof. Simon Benita (IIA grant number #65753). The Authors appreciate very much the assistance of Dr Ofir Tirosh, the Anayltical Geochemistry laboratory, The Institute of Earth Scienses, The Hebrew University of Jerusalem for the determination of the numerous Pt samples by ICP-MS.

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • Cytotoxicity
  • Efficacy
  • OPA platinum
  • Organ biodistribution
  • Pharmacokinetics
  • Subcellular localization
  • Xenograft cancer models

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