Loratadine self-microemulsifying drug delivery systems (SMEDDS) in combination with sulforaphane for the synergistic chemoprevention of pancreatic cancer

Pancreatic cancer (PC), currently the third leading cause of cancer-related deaths in the USA, is projected to become the second leading cause, behind lung cancer, by 2020. The increasing incidence, low survival rate, and limited treatment opportunities necessitate the use of alternative approaches such as chemoprevention, to tackle PC. In this study, we report significant synergistic chemoprevention efficacy for the first time from a low-dose combination of a classical antihistaminic drug, Loratadine (LOR) and a neutraceutical compound, Sulforaphane (SFN) using a self-microemulsifying drug delivery system (SMEDDS) formulation. The formulation was developed using Quality by Design approach (globule size, 95.13 +/- 7.9nm; PDI, 0.17 +/- 0.04) and revealed significant (p<0.05) enhancement in the in vitro dissolution profile confirming the enhanced solubility of BCS class II drug LOR with SMEDDS formulation. The LOR-SFN combination revealed similar to 40-fold reduction in IC50 concentration compared to LOR alone in MIA PaCa-2 and Panc-1 cell lines respectively, confirming the synergistic enhancement in chemoprevention. Further, the nanoformulation resulted in similar to 7-fold and similar to 11-fold reduction in IC50 values compared to LOR-SFN combination. Hence, our studies successfully demonstrate that a unique low-dose combination of LOR encapsulated within SMEDDs with SFN shows significantly enhanced chemopreventive efficacy of PC.