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. 2018 Oct 12;19(10):3132.
doi: 10.3390/ijms19103132.

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

Liang Li  1 , Na Liang  2 , Danfeng Wang  3 , Pengfei Yan  4 , Yoshiaki Kawashima  5 , Fude Cui  6 , Shaoping Sun  7
Affiliations

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

Liang Li et al. Int J Mol Sci. .

Abstract

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.

Keywords: amphiphilic polymer; chitosan; deoxycholic acid; folic acid; micelles; paclitaxel.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of the synthesis of FA-CS-DA (folic acid–chitosan–deoxycholic acid).
Figure 2
Figure 2
1H-NMR spectra of (a) CS, (b) CS-DA and (c) FA-CS-DA.
Figure 3
Figure 3
FTIR spectra of (a) CS, (b) CS-DA and (c) FA-CS-DA.
Figure 4
Figure 4
Variation of the fluorescence intensity ratio of I1/I3 against the logarithm of FA-CS-DA concentration.
Figure 5
Figure 5
Transmission electron microscopy (TEM) image of paclitaxel (PTX)-loaded FA-CS-DA micelles.
Figure 6
Figure 6
XRD spectra of (a) PTX, (b) a physical mixture of PTX and blank micelles, (c) PTX-loaded micelles and (d) blank micelles.
Figure 7
Figure 7
In vitro cytotoxicity of PTX-loaded FA-CS-DA micelles.
Figure 8
Figure 8
Tumors excised from the mice after intravenous injection treatment.
See this image and copyright information in PMC

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