Pluronic-poly (acrylic acid)-cysteine/Pluronic L121 mixed micelles improve the oral bioavailability of paclitaxel

Abstract

The aim of the study is to synthesize a thiolated Pluronic copolymer, Pluronic-poly (acrylic acid)-cysteine copolymer, to construct a mixed micelle system with the Pluronic-poly (acrylic acid)-cysteine copolymer and Pluronic L121 (PL121) and to evaluate the potential of these mixed micelles as an oral drug delivery system for paclitaxel. Compared with Pluronic-poly (acrylic acid)-cysteine micelles, drug-loading capacity of Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles was increased from 0.4 to 2.87%. In vitro release test indicated that Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles exhibited a pH sensitivity. The permeability of drug-loaded micelles in the intestinal tract was studied with an in situ perfusion method in rats. The presence of verapamil and Pluronic both improved the intestinal permeability of paclitaxel, which further certified the inhibition effect of thiolated Pluronic on P-gp. In pharmacokinetic study, the area under the plasma concentration-time curve (AUC0→∞) of paclitaxel-loaded mixed micelles was four times greater than that of the paclitaxel solution (p < 0.05). In general, Pluronic-poly (acrylic acid)-cysteine/PL121 micelles were proven to be a potential oral drug delivery system for paclitaxel.

Development and Characterization of Lecithin-based Self-assembling Mixed Polymeric Micellar (saMPMs) Drug Delivery Systems for Curcumin

“…Although the CMC of PLURONIC L121 is considered the lowest, and this surfactant can self-assemble into micelles, the PPO fragment is excessively long and has limited space for loading hydrophobic curcumin. Therefore, the micelles with PLURONIC L121 precipitated38394041. Combining TPGS and lecithin also caused precipitation.…”

A pre-formulation study of a polymeric solid dispersion of paclitaxel prepared using a quasi-emulsion solvent diffusion method to improve the oral bioavailability in rats

“…administration (2.5 mg/kg) of PTX solution (based on the TAXOL Õ ) was 2091.7 ± 414.5 h ng/mL (n ¼ 5) and the dose-normalized AUC 0-1 was greater than that of Gao et al 16 but less than that of Li et al 38 and Shanmugam et al 39 . The PK parameters (T 1/2 and AUC 0-1 ) of the oral administration of PTX solution were in line with that of the Zhao et al 40 . There was no significant difference between the two controls for oral administration, and there were no significant differences among all the groups in terms of T 1/2 and CL.…”

β-casein nanovehicles for oral delivery of chemotherapeutic drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells

“…Oral administration of PTX was recently examined using different vehicles, including glycyrrhizic acid micelles [ 42 ], pluronic-based micelles [ 43 , 44 ], chitosan-based nanovehicles [ 45 , 46 ] and lipid-based nanoparticles (NPs) [ 45 , 47 ]. However, none of these vehicles exhibited target-activated release in the stomach.…”