%P 219-226
%I Elsevier B.V.
%A M.R. Chowdhury
%A R.M. Moshikur
%A R. Wakabayashi
%A Y. Tahara
%A N. Kamiya
%A M. Moniruzzaman
%A M. Goto
%V 565
%T In vivo biocompatibility, pharmacokinetics, antitumor efficacy, and hypersensitivity evaluation of ionic liquid-mediated paclitaxel formulations
%L scholars11523
%J International Journal of Pharmaceutics
%O cited By 28
%R 10.1016/j.ijpharm.2019.05.020
%D 2019
%X In order to prevent common hypersensitivity reactions to paclitaxel injections (Taxol), we previously reported an ionic liquid-mediated paclitaxel (IL-PTX)formulation with small particle size and narrow size distribution. The preliminary work showed high PTX solubility in the IL, and the formulation demonstrated similar antitumor activity to Taxol, while inducing a smaller hypersensitivity effect in in vitro cell experiments. In this study, the stability of the IL-PTX formulation was monitored by quantitative HPLC analysis, which showed that IL-PTX was more stable at 4 °C than at room temperature. The in vivo study showed that the IL-PTX formulation could be used in a therapeutic application as a biocompatible component of a drug delivery system. To assess the in-vivo biocompatibility, IL or IL-mediated formulations were administered intravenously by maintaining physiological buffered conditions (neutral pH and isotonic salt concentration). From in vivo pharmacokinetics data, the IL-PTX formulation was found to have a similar systemic circulation time and slower elimination rate compared to cremophor EL mediated paclitaxel (CrEL-PTX). Furthermore, in vivo antitumor and hypersensitivity experiments in C57BL/6 mice revealed that IL-PTX had similar antitumor activity to CrEL-PTX, but a significantly smaller hypersensitivity effect compared with CrEL-PTX. Therefore, the IL-mediated formulation has potential to be an effective and safe drug delivery system for PTX. © 2019 Elsevier B.V.
%K paclitaxel; antineoplastic agent; cremophor; glycerol; ionic liquid; paclitaxel, allergic reaction; animal experiment; animal model; antineoplastic activity; area under the curve; Article; behavior change; biocompatibility; blood vessel permeability; cancer growth; cancer inhibition; cancer size; cell division; cell viability; complement activation; controlled study; drug delivery system; drug efficacy; drug elimination; drug formulation; drug retention; drug solubility; drug stability; female; follow up; high performance liquid chromatography; histamine release; hypersensitivity; in vitro study; in vivo study; mouse; nonhuman; particle size; priority journal; rate constant; survival time; animal; C57BL mouse; drug delivery system; drug hypersensitivity; intravenous drug administration; melanoma; skin tumor; tumor cell line, Administration, Intravenous; Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Drug Delivery Systems; Drug Hypersensitivity; Female; Glycerol; Ionic Liquids; Melanoma; Mice, Inbred C57BL; Paclitaxel; Skin Neoplasms