Liposome Formulation of Paclitaxel with Enhanced Solubility and Stability

Abstract

Despite its strong antitumor activity, paclitaxel (Taxol R ) has limited clinical applications due to its low aqueous solubility and hypersensitivity caused by Cremophor R EL and ethanol which is the vehicle used in the current commercial product. In an attempt to develop a pharmaceutically acceptable formulation that could replace Taxol R , a paclitaxel incorporated liposome has been constructed to improve solubility and physicochemical stability. The effect of various components of the liposome, including cholesterol and lipid, on the solubility and entrapment efficiency (EE) of paclitaxel was systematically investigated. The results showed that 5% (v/v) of polyethylene glycol 400 in the hydration medium of liposome significantly increased the solubility (up to 3.39 mg/mL) as well as the EE and the paclitaxel content in the liposome formulation composed of 10% (w/v) of S 100 PC with cholesterol (cholesterolto-lipid molar ratio = 10:90). When sucrose (sugar-to-lipid molar ratio = 2.3) was added as a lyoprotectant during the freeze-drying of the liposome, physicochemical stability of liposome was significantly improved. Moreover, the cytotoxicity of the final liposome formulation against MDA-MB-231 human breast cancer cell line was not significantly different from that of Taxol R . The enhanced aqueous solubility as well as the physicochemical stability of paclitaxel in the liposome formulation developed in this study could be a safer and effective alternative to the Cremophor R EL and ethanol formulation.

Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals

“…This result can be due to two different factors that characterize PTX: low aqueous solubility and high chemical stability. These two factors combined can explain the results because probably this drug is more persistent in the surfaces, resisting more easily to environment conditions and cleaning procedures (Yang et al 2007).…”

In vitro Evaluation of Antiproliferative Effects of Self-assembling Nanoemulsion of Paclitaxel on Various Cancer Cell Lines

“…Novel methods such as nanodelivery systems would also improve biodistribution of cancer drugs and the pharmacokinetic profile [25]. Paclitaxel is one such anti-neoplastic drug that is used in cancer therapy known for its aqueous insolubility [16,16], which, as a result, is associated with increased binding to blood protein limiting its ability in treatment of solid tumors [10,26]. Currently, paclitaxel is administered in two forms, one as Taxol that is formulated by dissolving the mixture of dehydrated ethanol and Cremophor EL and Abraxane, which is an albumin, based nanoparticle formulation [23,44].…”

“…These include drug delivery systems that are submicron sized particles (92 -200 nm), that can be made using a variety of materials and configurations such as but not limited to micelles, dendrimers, nanoemulsions, liposomes, viruses and organometallic compounds [9,10,24,26,27].…”

Cellular Uptake Mechanism of Paclitaxel Nanocrystals Determined by Confocal Imaging and Kinetic Measurement

“…This may be contributed by the absence of helper chemicals that are used in the conventional formulations for solubilizing and/or encapsulating poorly soluble drugs (3)(4)(5)(6)(7). Any side effects associated with carrier chemicals are completely eliminated in (pure) nanocrystal formulations.…”

“…Cellular Uptake Imaging of Nanocrystals KB cells were seeded in confocal petri dishes at a density of 2×10 5 cells/well and cultured for 24 h. After adhering to dish walls, the KB cells were incubated in FA-deficient RPMI 1640 medium with 100 μg/mL SRB-PTX-NCs at different durations (15, 30 min, 1, 2, and 3 h) or incubated for 3 h with the concentration of the nanocrystals varied (1,5,25, and 100 μg/mL). Additionally, the KB cells were incubated for 3 h in FA-deficient RPMI1640 medium with 100 μg/mL bare or surface-modified SRB-PTX-NCs (PEG-Dp-SRB-PTX-NCs, FA-PEG-Dp-SRB-PTX-NCs, PEG-SRB-PTX-NCs, FA-PEG-SRB-PTX-NCs, F 127 -SRB-PTX-NCs, and F 68 -SRB-PTX-NCs).…”