Deoxycholic acid-grafted PEGylated chitosan micelles for the delivery of mitomycin C

Abstract

Mitomycin C (MTC) was incorporated to a micelle system preparing from a polymer named deoxycholic acid chitosan-grafted poly(ethylene glycol) methyl ether (mPEG-CS-DA). mPEG-CS-DA was synthesized and characterized by ¹H nuclear magnetic resonance (¹H-NMR) and Fourier transform infrared spectroscopy. mPEG-CS-DA formed a core-shell micellar structure with a critical micelle concentration of 6.57 µg/mL. The mPEG-CS-DA micelles were spherical with a hydrodynamic diameter of about 231 nm. After poly(ethylene glycol)ylation of deoxycholic acid chitosan (CS-DA), the encapsulation efficiency and drug loading efficiency increased from 50.62% to 56.42% and from 20.51% to 24.13%, respectively. The mPEG-CS-DA micelles possessed a higher drug release rate than the CS-DA micelles. For pharmacokinetics, the area under the curve (AUC) of the mPEG-CS-DA micelles was 1.5 times higher than that of MTC injection, and these micelles can enhance the bioavailability of MTC. mPEG-CS-DA micelles reduced the distribution of MTC in almost all normal tissues and had the potential to improve the kidney toxicity caused by MTC injection.

• Biodistribution
• mitomycin C
• pharmacokinetics
• polymeric micelles
• synthesis

Declaration of interest

The authors report no conflicts of interest in this work.

This work was supported by the Jilin Province Science and Technology Development Foundation of China (No. 200705414 and No. 20120947), the Jilin Province Science and Technology Research Foundation of China (No. 2008263) and the National Natural Science Foundation of China (No. 21102055).