Rational design of polymer-lipid nanoparticles for docetaxel delivery

In this work, a stable nanocarrier for the anti-cancer drug docetaxel was rational designed. The nanocarrier was developed based on the solid lipid nanoparticle preparation process aiming to minimize the total amount of excipients used in the final formulations. A particular interest was put on the effects of the polymers in the final composition. In this direction, two poloxoamers -Pluronic F127 and F68- were selected. Some poloxamers are well known to be inhibitors of the P-glycoprotein efflux pump. Additionally, their poly-ethylene-oxide blocks can help them to escape the immune system, making the poloxamers appealing to be present in a nanoparticle designed for the treatment of cancer. Within this context, a factorial experiment design was used to achieve the most suitable formulations, and also to identify the effects of each component on the final (optimized) systems. Two final formulations were chosen with sizes < 250 nm and PDI < 0.2. Then, using dynamic light scattering and nanotracking techniques, the stability of the formulations was assessed during six months. Structural studies were carried on trough different techniques: DSC, x-ray diffraction, FTIR-AR and Molecular Dynamics. The encapsulation efficiency of the anticancer drug docetaxel (> 90%) and its release dynamics from formulations were measured, showing that the polymer-lipid nanoparticle is suitable as a drug delivery system for the treatment of cancer. (AU)