DEVELOPMENT, EVALUATION AND TARGETING OF IMATINIB MESYLATE LOADED SOLID LIPID NANOPARTICLES TO THE LYMPHATIC SYSTEM

For a formulation scientist, the delivery of therapeutic agents to the diseased organ has been a challenging problem. It is expected to improve the therapeutic index and reduce side effects of a drug by good delivery strategy to diseased organ. The objective of this investigation is to evaluate the targeting potential of solid lipid nanoparticle (SLN) formulation of imatinib mesylate to the lymphatic system using response surface methodology of design of experiment. Box-Behnken DOE was constructed using imatinib mesylate, compritol 888 ATO (X1) and pluronic F68 (X2) as independent factors and particle size (Y1) and entrapment efficiency (Y2) as dependant factors. The SLN formulation was prepared by hot homogenization followed by ultrasonication. Prepared SLN were analyzed by FTIR, DSC, DLS, PXRD and SEM. The optimized particle size and entrapment efficiency of the imatinib mesylate loaded solid lipid nanoparticle was found to be 190 nm and 62.5% respectively, which are sufficient to reach lymphatic system. FTIR revealed no interaction between imatinib mesylate and compritol 888 ATO. Compritol 888 ATO retained its crystalline nature in the imatinib mesylate loaded SLN formulation revealed by DSC study. The results showed that pharmacokinetic parameters such as area under the whole blood concentration- time curve, Cmax, Tmax were significantly different (P<0.05) compared with standard imatinib mesylate oral suspension and the targeting efficiency of both imatinib mesylate loaded SLN and the standard suspension at the mesenteric lymph node significantly increased (P<0.05).