Preparation and Optimization Lipid Nanocapsules to Enhance the Antitumor Efficacy of Cisplatin in Hepatocellular Carcinoma HepG2 Cells.

This work aimed to develop and optimize several lipid nanocapsule formulations (LNCs) to encapsulate cisplatin (CDDP) for treatment of hepatocellular carcinoma. By comparing the effect of oil/surfactant ratio, lecithin content, and oil/surfactant type on LNC characteristics, two LNCs were selected as optimal formulations: HS15-LNC (Solutol HS 15/MCT/lecithin, 54.5:42.5:3%, w/w) and EL-LNC (Cremophor EL/MCT/lecithin, 54.5:42.5:3%, w/w). Both LNCs could effectively encapsulate CDDP with the encapsulation efficiency of 73.48 and 78.84%. In vitro release study showed that both LNCs could sustain the release CDDP. Moreover, cellular uptake study showed that C6-labeled LNCs could be effectively internalized by HepG2 cells. Cellular cytotoxicity study revealed that both LNCs showed negligible cellular toxicity when their concentrations were below 313 µg/mL. Importantly, CDDP-loaded LNCs exhibited much stronger cell killing potency than free CDDP, with the IC50 values decreased from 17.93 to 3.53 and 5.16 µM after 72-h incubation. In addition, flow cytometric analysis showed that the percentage of apoptotic cells was significantly increased after treatment with LNCs. Therefore, the prepared LNC formulations exhibited promising anti-hepatocarcinoma effect, which could be beneficial to hepatocellular carcinoma therapy.

Poly(D, L-lactide-co-glycolide)/montmorillonite nanoparticles for improved oral delivery of exemestane.

The aim of this study was to develop poly(D,L-lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles formulations for improved oral delivery of exemestane. Exemestane-loaded PLGA nanoparticles and PLGA/MMT nanoparticles were prepared by a modified solvent extraction/evaporation technology with vitamin E succinated polyethylene glycol 1000 (TPGS) as emulsifier. The content of MMT was estimated by thermal gravimetric analysis. The drug encapsulation efficiency and in vitro drug release kinetics were measured by high-performance liquid chromatography. The size, size distribution, surface charge and morphology of the exemestane-loaded nanoparticles were characterized using a Zetasizer Nano ZS and field emission scanning electron microscopy. The physical status of exemestane in the nanoparticles was characterized by differential scanning calorimetry. In vitro cellular uptake of coumarin-6-loaded nanoparticles was investigated by confocal laser scanning microscope, demonstrating that the fluorescence nanoparticles were internalized by Caco-2 cells (as an in vitro gastrointestinal model). The results of in vitro cytotoxicity experiment on MCF-7 cells (as a model of breast cancer cells) showed the exemestane-loaded nanoparticles resulted in lower cell viability versus the pure exemestane solution. The cytotoxicity against MCF-7 cells for exemestane-loaded nanoparticles and pure exemestane solution was dependent on the drug concentration and incubation time. In conclusion, this study indicates the capability of PLGA nanoparticles and PLGA/MMT nanoparticles in enhancing the oral delivery of exemestane.