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

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.

Synthesis and characterization of amphiphilic glycidol-chitosan-deoxycholic acid nanoparticles as a drug carrier for doxorubicin.

Novel amphiphilic chitosan derivatives (glycidol-chitosan-deoxycholic acid, G-CS-DCA) were synthesized by grafting hydrophobic moieties, deoxycholic acid (DCA), and hydrophilic moieties, glycidol, with the purpose of preparing carriers for poorly soluble drugs. Based on self-assembly, G-CS-DCA can form nanoparticles with size ranging from 160 to 210 nm, and G-CS-DCA nanoparticles maintained stable structure for about 3 months when stored in PBS (pH 7.4) at room temperature. The critical aggregation concentration decreased from 0.043 mg/mL to 0.013 mg/mL with the increase of degree of substitution (DS) of DCA. Doxorubicin (DOX) could be easily encapsulated into G-CS-DCA nanoparticles and keep a sustained release manner without burst release when exposed to PBS (pH 7.4) at 37 °C. Antitumor efficacy results showed that DOX-G-CS-DCA have significant antitumor activity when MCF-7 cells were incubated with different concentration of DOX-G-CS-DCA nanoparticles. The fluorescence imaging results indicated DOX-G-CS-DCA nanoparticles could easily be uptaken by MCF-7 cells. These results suggested that G-CS-DCA nanoparticles may be a promising carrier for DOX delivery in cancer therapy.

Preparation and characterization of nanoaggregates self-assembled by lithocholic acid and N-trimethyl modified chitosan derivatives.

A novel kind of chitosan derivatives (CS-LA-TM) were synthesized by grafting hydrophobic molecules of lithocholic acid (LA) and quaternization. CS-LA-TM and micelle-like self-aggregates were characterized by FTIR, 1H NMR, fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). The critical micelles concentration (CMC) ranging from 0.009 mg/mL to 0.030 mg/mL decreased with increasing of the degree of substitution (DS) of LA, pH of medium but with decreasing of the degree of quaternization (DQ) of amino groups. The TEM images demonstrated that spherical CS-LA-TM nanoaggregates with uniform size were formed by self-assembly. The sizes (100-200 nm) of CS-LAs-TMs nanoaggregates increased with increasing of DS, DQ, and can be easily controlled by pH of medium, which may confer the nanoaggregates potential as delivery systems for anticancer drugs, or DNA and siRNA.