Camptothecin (CPT) and its analogs exhibit remarkable anti-tumor activity, due to their ability to inhibit DNA topoisomerase I. However, its use is limited by the lack of solubility and stability of the active lactone form. An attractive alternative is the encapsulation of CPT within liposomes. In this study, CPT was incorporated into solid lipid nanoparticles (SLN) based on the triglyceride, Compritol 888 ATO, using supercritical fluid technology without requiring the use of harmful solvents. This drug delivery system was characterized and its cytotoxicity effect was evaluated by measuring MCF7 and MCF10A cell viability as a function of drug loading during a 48-h treatment. Results showed that after 10 h of treatment, MCF7 cells displayed an IC50 of 0.23±0.034 μM at a 1:5 (CPT:SLN) loading and 0.22±0.027 μM at a 1:10 loading, whereas MCF10A cells displayed an IC50 of 0.40±0.036 μM at 1:5 and 0.60±0.063 μM at 1:10. On the other hand, the IC50 of free CPT was 0.57±0.035 μM and 1.07±0.077 μM for MCF7 and MCF10A cells, respectively. Cellular uptake and retention measurements in both cells displayed a two-fold increase when using the SLN formulation. The results from this study showed that the cytotoxic effects of CPT in a SLN formulation improved when compared with those seen with free CPT. The results of this study showed that delivery of CPT as a SLN formulation could be a promising strategy for enhancing its chemotherapeutic effects.