The distribution of therapeutic drugs to the sick organ has proven to be a difficult issue for formulation scientists. A good drug delivery approach to the sick organ is intended to lessen side effects and improve the therapeutic index. This study aims to assess the ability of doxorubicin loaded solid lipid nanoparticle (SLN) formulation to target the lymphatic system through the use of response surface methodology in experiment design. Doxorubicin, Compritol 888 ATO (X1), and Pluronic F68 (X2) were used as independent elements in the construction of the Box Behnken DOE, whereas particle size (Y1) and entrapment efficiency (Y2) were used as dependent factors. Hot homogenization and ultrasonication were used to create the SLN formulation. The produced SLN was analysed using FTIR and SEM. The solid lipid nanoparticle loaded with doxorubicin was found to have an optimised particle size of 190 nm and an entrapment effectiveness of 6 6 58 %, respectively. These values are adequate for the particle to reach the lymph atic system. No interaction between doxorubicin and Compritol 888 ATO was detected by FTIR. The results demonstrated that the targeting efficiency of both the standard oral suspension and the doxorubicin loaded SLN at the mesenteric lymph node increased si gnificantly (P<0.05), as did the pharmacokinetic parameters, such as area under the whole blood concentration time curve, Cmax, and Tmax.