Thermosensitive Depot-Forming Injectable Phosphatidylcholine Blends Tailored for Localized Drug Delivery

A thermosensitive depot-forming system was developed for sustained and localized delivery of the anticancer drug, paclitaxel. The formulation is injectable as a melt slightly above the body temperature and forms a solid depot upon cooling to 37°C. The thermosensitive system was prepared by blending various combinations of phosphatidylcholines at specific weight ratios solubilized in laurinaldehyde. Of the blends investigated, distearoyl-phosphatidylcholine (DSPC) and egg-phosphatidylcholine (ePC) were found to be most miscible. A liquid-to-gel phase transition temperature (TC) of 39°C was observed for the 70:30 (w/w) DSPC-ePC blend and a TC of 38.4°C with the addition of paclitaxel. Blends containing higher concentrations of ePC had a greater degree of swelling and weight loss. Furthermore, microscopy revealed an increase in porosity and erosion as the amount of ePC was increased in blends incubated in biologically relevant media. DSPC-ePC blends provided sustained release of paclitaxel over a 30-day period and the rate of drug release increased as the amount of ePC increased. Overall, the relationships established between the composition and properties of the blend may be employed to tailor the thermosensitive injectable formulation for localized chemotherapy of solid tumors. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3623-3631, 2013