NIR-responsive ROS generating core and ROS-triggered 5'-Deoxy-5-fluorocytidine releasing shell structured water-swelling microgel for locoregional combination cancer therapy.

Combination chemotherapy now becomes the most standard cancer treatment protocol. Here, we present a core-shell type polymeric microgel (CSPM) which combines photodynamic and chemo therapeutic modalities in one-pot system. CSPM localizes in the malignant lesion after intratumoral injection, releases reactive oxygen species (ROS) and anticancer drug (5'-deoxy-5-fluorocytidine; DFCR) under the near-infrared (NIR) laser treatment. Pheophorbide A (PheoA)-linked poly(hydroxyethyl methacrylate) (poly-HEMA) was designated to a ROS-generating core, and chemically covered with a chitosan shell. In addition, phenylboronic acid was employed in chitosan shells and linked to DFCR to form an ROS cleavable boronic ester. The core-shell structure of CSPM was determined by transmission electron microscopy. NIR-responsive photodynamic ROS generation was confirmed by the oxidative reduction of 9,10-dimethylanthracene (a fluorescent dye), and the cascadic release of DFCR by ROS was confirmed by a release study and a live and dead cell imaging study. Typically, poly-HEMA cored microgel increased its volume by 48.9-fold after absorption of body fluid. This swelling property ensured CSPM was retained in tumor tissues after subtumoral injection and the suitability of CSPM for locoregional phototherapy. The therapeutic effect of CSPM was attributed to the combined, cascadic deliveries of cytotoxic ROS and DFCR and confirmed by growth inhibition studies in in vitro pancreatic cancer cells and in vivo colon cancer mouse model.

Formulation parameters influencing the physicochemical characteristics of rosiglitazone-loaded cationic lipid emulsion.

To enhance the solubility of rosiglitazone, rosiglitazone-loaded cationic lipid emulsion was formulated using cationic lipid DOTAP, DOPE, castor oil, tween 20, and tween 80. The formulation parameters in terms of droplet size were optimized focused on the effect of the cationic lipid emulsion composition ratio on drug encapsulating efficiency, in vitro drug release, and cellular uptake of the rosiglitazone-loaded emulsion. Droplet sizes of a blank cationic emulsion and a rosiglitazone-loaded cationic emulsion ranged between 195-230 nm and 210-290 nm, respectively. The encapsulation efficiency of the rosiglitazone-loaded emulsion was more than 90%. The rosiglitazone-loaded cationic emulsion improved in vitro drug release over the drug alone and showed a much higher cellular uptake than rosiglitazone alone. Moreover, drug loading in cationic emulsions increased cellular uptake of rosiglitazone in insulin-resistant HepG2 cells more than the normal HepG2 cells. Taken together, these results indicate that cationic lipid emulsions could be a potential delivery system for rosiglitazone and could enhance its cellular uptake efficiency into target cells.