Preparation and in vitro antiproliferative effect of tocotrienol loaded lipid nanoparticles

Abstract The primary objective of this study was to prepare nanostructured lipid carriers loaded with tocotrienol-rich-fraction of palm oil (TRF-NLCs) and to evaluate their antiproliferative effects against neoplastic +SA mammary epithelial cells. This necessitated optimizing the ultrasonic homogenization process parameters and the surfactant to lipid ratio within the NLCs. Therefore, sonication time and pulsar rate were initially evaluated for their effect on the size and polydispersity of the nanoparticles using a full factorial design. Also, varying the surfactant to lipid ratio from 0.25:1 to 3:1 was evaluated for its effect on the same responses. Optimal nanoparticles were obtained when dispersions containing a surfactant to lipid ratio of 0.5:1, with a total lipid concentration of 0.25 (w/v), were sonicated at 60% pulsar rate for 10 min. These parameters were subsequently used to prepare TRF-NLCs. TRF was loaded into the nanoparticles by substituting 10% (TRF-10-NLC) or 50% (TRF-50-NLC) of the lipid phase with TRF. In an extended stability study, no significant change in particle size of the TRF-NLCs was observed over 6 months of storage. In the cell culture studies, TRF-NLCs were shown to exhibit potent antiproliferative effect against neoplastic +SA mammary epithelial cells. The IC 50 values of TRF-10-NLCs were 2-fold lower than the IC 50 value of the reference TRF/BSA solution. In contrast, TRF-50-NLCs had comparable IC 50 values as the TRF/BSA solution, which signified the importance of TRF encapsulation within NLCs on their activity. Furthermore, these findings suggested that TRF-NLCs may have potential value in the treatment of breast cancer.