pH-sensitive chitosan-derived nanoparticles as doxorubicin carriers for effective anti-tumor activity: preparation and in vitro evaluation.

pH-sensitive self-aggregated nanoparticles (SNPs), based on amphiphilic deoxycholic acid (DOCA) modified carboxymethyl chitosan (DCMC), were prepared for delivery of the anticancer drug doxorubicin (DOX). DCMCs with different degrees of substitution (DS) of DOCA were initially synthesized and characterized. Based on self-aggregation, DCMC formed nanoparticles with size ranging from 87 to 174 nm. The critical aggregation concentration (CAC) decreased on increasing the DS of DOCA. Moreover, the DCMC SNPs showed an acidic pH-induced aggregation and deformation behavior. The DOX-loaded SNPs ([D]NP) exhibited a sustained drug release manner, which could be accelerated by an acidic pH, but delayed by a higher DS of DOCA. Antitumor efficacy results showed that [D]NP could suppress both sensitive and resistant MCF-7 cells effectively in a dose- and time-dependent manner. The enhanced cellular uptake and greater retention of [D]NP in drug-resistant cells, as evidenced by confocal microscopy and flow cytometry, contributed to a superior efficacy of [D]NP over free DOX. These results suggest the potential of DCMC SNPs as carriers for the hydrophobic drug DOX for effective cancer therapy against drug-resistant tumors.

Preparation and characterization of ß-elemene-loaded microemulsion.

Intravenously injectable emulsion of ß-elemene was studied in detail. Both blank and ß-elemene-loaded microemulsions were prepared using a simple water titration method. The pseudoternary phase diagram was constructed for the optimization of microemulsion. The loading capacity test, dilutability test, and especially the influence of antioxidants were conducted for further optimization of ß-elemene-loaded microemulsion. Transmission electron microscope showed intact and spherical microemulsion droplets. Conductivity and viscosity measurements were used to study the phase behaviors of ß-elemene-loaded microemulsions, providing convincing explanation. In vitro release study showed that ß-elemene was steadily released until 12 h, which most fitted the first order.

[Preparation of adriamycin-loaded temperature/pH sensitive self-assembly block copolymer micelles].

The dialysis method was employed to load adriamycin into the micelles formed by temperature and pH sensitive polyhistidine-co-DL-lactide-co-glycolide-polyethylene glycol poly DL-lactide-co-glycolide-co-histidine (OLH-b-PLGA-b-PEG-b-PLGA-b-OLH). The critical micelle concentration (CMC) of the copolymer was measured with pyrene fluorescent probe method under different temperatures. The entrapment rate and drug-loading rate were determined with dialysis method. The diameter, morphology and surface potential of the copolymer micelles were investigated by corresponding instruments, respectively. The release behavior of adriamycin from copolymer micelles and the pH sensitivity were studied. The CMC of the copolymers ranged from 0.022 4 to 0.001 7 microg x mL(-1). The entrapment rate and drug-loading rate were 92.8% and 15.7%, respectively. The micelles have a mean diameter of (61.7 +/- 13.4) nm, and zeta potential was -9.88 mV. The in vitro adriamycin release rate increased with the pH dropping from 7.4 to 5.0. The results indicated that the CMC of the copolymers decreased as the raising of temperature, drug release behavior from the micelles possessed clearly pH sensitivity, and the copolymers may have a potential in targeted delivery system for anticancer drugs.