Preparation of sodium cholate-based micelles through non-covalent ıbonding interaction and application as oral delivery systems for paclitaxel

Abstract

In present study, two types of micelles based on sodium cholate (NaC) were prepared through non-covalent bonding interaction and the potential of micelles as oral drug delivery systems for paclitaxel (PTX) was evaluated. Pluronic–chitosan (F127–CS) and Pluronic–poly (acrylic acid) (F127–PAA) copolymers were synthesized. Electrostatic interaction and hydrogen bond were used to prepare F127–CS/NaC micelles and F127–PAA/NaC micelles, respectively. The physicochemical characteristics of micelles were determined. An average diameter of 67.5 nm and unimodal pattern of size distribution were observed for F127–CS/NaC micelles. While for F127–PAA/NaC micelles, an average diameter of 85.89 nm and non-unimodal pattern of size distribution were observed. The results revealed that F127–CS/NaC micelles were more integrated than F127–PAA/NaC micelles. Further experiments showed that the F127–CS/NaC micelles had a higher drug-loading content of 12.8% and a lower critical micelle concentration (CMC) of 2.5 × 10⁻³mol/L compared with F127–PAA/NaC micelles. In vitro cytotoxicity analysis demonstrated that the PTX-loaded F127–CS/NaC micelles were of great efficiency in inhibiting the growth of drug-resistant breast cancer MCF-7 cells (MCF-7/Adr). The intragastric administration of the PTX-loaded F127–CS/NaC micelles in rats provided a 4.33-fold higher absolute bioavailability compared to commercial Taxol®, indicating an efficient oral absorption of PTX delivered by micelles. These findings signify that F127–CS/NaC micelle may be a promising carrier for the delivery of PTX.

Keywords:

• Non-covalent interaction
• oral absorption
• paclitaxel
• Pluronic F127
• sodium cholate

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by Natural Science Foundation for Young Scholar of Shandong Province (ZR2013HQ011) and Scientific Research Foundation for Returned Scholars, Ministry of Education of China.