Preparation of Cationic Amphiphilic Nanoparticles with Modified Chitosan Derivatives for Doxorubicin Delivery

Xiudong Liu,Xiaojun Ma,Xin Xiong,Weiting Yu,Rumen Krastev,Huofei Zhou

doi:10.3390/ma14227010

Abstract

Polymeric micelle-like nanoparticles have demonstrated effectiveness for the delivery of some poorly soluble or hydrophobic anticancer drugs. In this study, a hydrophobic moiety, deoxycholic acid (DCA) was first bonded on a polysaccharide, chitosan (CS), for the preparation of amphiphilic chitosan (CS-DCA), which was further modified with a cationic glycidyltrimethylammounium chloride (GTMAC) to form a novel soluble chitosan derivative (HT-CS-DCA). The cationic amphiphilic HT-CS-DCA was easily self-assembled to micelle-like nanoparticles about 200 nm with narrow size distribution (PDI 0.08–0.18). The zeta potential of nanoparticles was in the range of 14 to 24 mV, indicating higher positive charges. Then, doxorubicin (DOX), an anticancer drug with poor solubility, was entrapped into HT-CS-DCA nanoparticles. The DOX release test was performed in PBS (pH 7.4) at 37 °C, and the results showed that there was no significant burst release in the first two hours, and the cumulative release increased steadily and slowly in the following hours. HT-CS-DCA nanoparticles loaded with DOX could easily enter into MCF-7 cells, as observed by a confocal microscope. As a result, DOX-loaded HT-CS-DCA nanoparticles demonstrated a significant inhibition activity on MCF-7 growth without obvious cellular toxicity in comparison with blank nanoparticles. Therefore, the anticancer efficacy of these cationic HT-CS-DCA nanoparticles showed great promise for the delivery of DOX in cancer therapy.

Highlights

Most anticancer drugs are poorly soluble, which gives rise to considerable challenges for their clinical application
We successfully developed a novel cationic soluble amphiphilic chitosan derivatives
Based on self−assembly, the cationic amphiphilic HT-CS-deoxycholic acid (DCA) nanoparticles were spherical in shape, with an average size around 200 nm and zeta potential ranging from 14 to

Summary

Introduction

Most anticancer drugs are poorly soluble, which gives rise to considerable challenges for their clinical application. To promote the solubility of drugs, some surfactants such as Cremophor EL/ethanol, and Tween 80 are usually used. These reagents, can cause several side effects on the liver and kidneys, and cause dose-dependent hemolysis and acute hypersensitivity reactions [1]. Numerous nanocarriers for the delivery of poorly soluble or hydrophobic drugs have been developed, such as polymeric nanoparticles, liposomes, hydrogels, and mesoporous silica nanoparticles. Polymeric micelle-like nanoparticles self-assembled from biodegradable and biocompatible amphiphilic block copolymers and hydrophobically modified water-soluble polymers have been extensively investigated for drug delivery application [6,7,8]. The cationic polymeric nanoparticles usually display good water solubility and high cellular uptake efficiency [9]

Methods

Discussion

Conclusion