| 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
|
| Resource |
| Human and Animal Cells |
B16 F10(RCB2630) |
