Day: January 2, 2019

Amphiphilic Polymeric Micelles Based on Deoxycholic Acid and Folic Acid Modified Chitosan for the Delivery of Paclitaxel

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The present investigation aimed to develop a tumor-targeting drug delivery system for paclitaxel (PTX). The hydrophobic deoxycholic acid (DA) and active targeting ligand folic acid (FA) were used to modify water-soluble chitosan (CS). As an amphiphilic polymer, the conjugate FA-CS-DA was synthesized and characterized by Proton nuclear magnetic resonance (¹H-NMR) and Fourier-transform infrared spectroscopy (FTIR) analysis. The degree of substitutions of DA and FA were calculated as 15.8% and 8.0%, respectively. In aqueous medium, the conjugate could self-assemble into micelles with the critical micelle concentration of 6.6 × 10-3 mg/mL. Under a transmission electron microscope (TEM), the PTX-loaded micelles exhibited a spherical shape. The particle size determined by dynamic light scattering was 126 nm, and the zeta potential was +19.3 mV. The drug loading efficiency and entrapment efficiency were 9.1% and 81.2%, respectively. X-Ray Diffraction (XRD) analysis showed that the PTX was encapsulated in the micelles in a molecular or amorphous state. In vitro and in vivo antitumor evaluations demonstrated the excellent antitumor activity of PTX-loaded micelles. It was suggested that FA-CS-DA was a safe and effective carrier for the intravenous delivery of paclitaxel.

Deoxycholic acid (DA) is a typical bile acid that is secreted from the gallbladder to emulsify fats and other hydrophobic compounds. As an endogenous compound with a lipophilic nature, the introduction of DA to CS could adjust the hydrophilicity/hydrophobicity balance of the conjugate and would not lead to any serious toxicity. DA has been approved as an excellent pharmaceutical additive for injection. Molecular ligands were often grafted onto drug carriers to develop tumor-targeted drug delivery systems. It has been reported that folate receptors are over-expressed in many types of cancers, while almost undetectable in healthy tissues. The folic acid-modified nanocarriers could improve therapeutic efficacy via folate receptor-mediated active targeting. The antitumor efficiency could be significantly enhanced by synergetic active and passive tumor targeting. Based on the above, in present study, a biocompatible nanocarrier based on deoxycholic acid and folic acid-modified chitosan (FA-CS-DA) was designed for targeting the delivery of PTX. The synthesis, characterization and self-assembly of FA-CS-DA and the characterization and in vitro/in vivo antitumor activity of PTX-loaded micelles were studied in detail. (Int J Mol Sci. 2018 Oct 12;19(10).)