Ionic-Liquid-Based Paclitaxel Preparation: A New Potential Formulation for Cancer Treatment

Abstract

Paclitaxel (PTX) injection (i.e., Taxol) has been used as an effective chemotherapeutic treatment for various cancers. However, the current Taxol formulation contains Cremophor EL, which causes hypersensitivity reactions during intravenous administration and precipitation by aqueous dilution. This communication reports the preliminary results on the ionic liquid (IL)-based PTX formulations developed to address the aforementioned issues. The formulations were composed of PTX/cholinium amino acid ILs/ethanol/Tween-80/water. A significant enhancement in the solubility of PTX was observed with considerable correlation with the density and viscosity of the ILs, and with the side chain of the amino acids used as anions in the ILs. Moreover, the formulations were stable for up to 3 months. The driving force for the stability of the formulation was hypothesized to be the involvement of different types of interactions between the IL and PTX. In vitro cytotoxicity and antitumor activity of the IL-based formulations were evaluated on HeLa cells. The IL vehicles without PTX were found to be less cytotoxic than Taxol, while both the IL-based PTX formulation and Taxol exhibited similar antitumor activity. Finally, in vitro hypersensitivity reactions were evaluated on THP-1 cells and found to be significantly lower with the IL-based formulation than Taxol. This study demonstrated that specially designed ILs could provide a potentially safer alternative to Cremophor EL as an effective PTX formulation for cancer treatment giving fewer hypersensitivity reactions.

Ionic Liquid-In-Oil Microemulsions Prepared with Biocompatible Choline Carboxylic Acids for Improving the Transdermal Delivery of a Sparingly Soluble Drug

“…Despite having various advantages, the use of ILs is limited because of their high toxicity and low biocompatibility and degradability [17]. In fact, most of the ILs used in previous studies, including imidazolium, pyridinium, and quinolinium cations and high strength inorganic acid anion-based ILs cannot be used in clinical applications because of their high toxicity and low biocompatibility [18,19]. Interestingly, ILs containing choline and amino acid esters as cations and organic acid anions (e.g., acetate, phosphate, and carboxylate) are non-toxic, biocompatible, and biodegradable [10,18,20].…”

Comparison of Ionic Liquids and Chemical Permeation Enhancers for Transdermal Drug Delivery

“…[30] A polar hydroxyl group attached to the cation can further enhance biocompatibility. Therefore cholinium, the cation corresponding to choline, an essential micronutrient, [30] was used in many ILs/DESs. [5][6][7][8][9][10][11][12] A total of 31 ILs/DESs were studied and a complete list of their compositions is provided in Table S1, Supporting Information.…”

Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach

“…Interestingly, hybrid ionic liquids contain active pharmaceutical ingredients and ionic liquids, which are promising strategies to improve their solubility, bioavailability, and biological effects. For instance, ionic liquid-based formulations enhanced the solubility and anticancer activities of several compounds, such as curcumin and paclitaxel [ 248 , 249 ]. Rutin-loaded ionic liquid–NPs were fabricated by a double-emulsion method and were found to exhibit cytotoxic effects against 786-O human renal cancer cells through amplifying sub-G1 population.…”