RRC ID 57784
Author Chowdhury MR, Moshikur RM, Wakabayashi R, Tahara Y, Kamiya N, Moniruzzaman M, Goto M.
Title In vivo biocompatibility, pharmacokinetics, antitumor efficacy, and hypersensitivity evaluation of ionic liquid-mediated paclitaxel formulations.
Journal Int J Pharm
Abstract 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.
Volume 565
Pages 219-226
Published 2019-6-30
DOI 10.1016/j.ijpharm.2019.05.020
PII S0378-5173(19)30373-4
PMID 31077761
MeSH Administration, Intravenous Animals Antineoplastic Agents, Phytogenic / administration & dosage* Antineoplastic Agents, Phytogenic / pharmacokinetics Cell Line, Tumor Drug Delivery Systems* Drug Hypersensitivity Female Glycerol / administration & dosage Glycerol / analogs & derivatives* Glycerol / pharmacokinetics Ionic Liquids / administration & dosage* Ionic Liquids / pharmacokinetics Melanoma / drug therapy Mice, Inbred C57BL Paclitaxel / administration & dosage* Paclitaxel / pharmacokinetics Skin Neoplasms / drug therapy
IF 4.845
Times Cited 5
Human and Animal Cells B16 F10(RCB2630)