Preparation of Doxorubicin- and Psoralen-Loaded Nanostructured Lipid Carrier and Its Multidrug Resistance Reversal Study

Multidrug resistance (MDR) is the major cause of tumor chemotherapy failure. This study aimed to combine doxorubicin with the MDR-reversal agent psoralen (PSO) by loading them into a nanostructured lipid carrier (NLC) to enhance the reversal activity of PSO and DOX. PSO-DOX-NLC was prepared based on the method of emulsification evaporation-low-temperature solidification. A central composite design and response-surface-optimization methodology were adopted to generate the optimal formulation of PSO-DOX-NLC. The encapsulation efficiency, morphology, zeta potential, particle size, in vitro release, differential scanning calorimetry (DSC), and infrared-spectroscopy properties, and reversal effect of PSO-DOX-NLC were also studied. The NLC prepared for this process was round and uniform in size and zeta potential; it's optimal formulation was 130 mg of lipid, 1.83:1 lecithin-to-lipid ratio, and 2.6% emulsifier. In vitro release data indicated that PSO-DOX-NLC had an apparent slow-release effect. Infrared spectra and DSC data showed that PSO-DOX-NLC may have formed a noncrystalline structure in the NLC system. The IC50 values of PSO/DOX, DOX-NLC, and PSO/DOX-NLC were 2.448, 0.965, and 0.379 mu g/mL respectively, proving that PSO-DOX-NLC can improve the reversal activity.