Summary: Pancreatic cancer remains refractory to current standards-of-care. Here, we first report that combination of a classical antihistaminic drug, Loratadine (LOR), and a neutraceutical compound, Sulforaphane (SFN), elicits remarkably synergistic chemo-preventive action on pancreatic cancer cells in vitro. However, LOR belongs to BCS class II exhibiting low solubility and high permeability that results in poor oral bioavailability. To address this limitation, we have developed a self-microemulsifying drug delivery system (SMEDDS) formulation carrying LOR, using Quality by Design approach (globule size, 95.13 ± 7.9 nm; PDI, 0.17 ± 0.04), and confirmed that this nanoformulation provides significantly enhanced dissolution profile of LOR in vitro. Further, the nanoformulation, in conjunction with SFN, provided in ~ 7-fold and ~ 11-fold reduction in IC50 values compared to free drug LOR-SFN combination in MIA PaCa-2 and Panc-1 cell lines, respectively. Hence, our studies successfully demonstrate that a unique low-dose combination of LOR encapsulated within SMEDDS with SFN shows significantly enhanced chemo-preventive efficacy in pancreatic cancer.
This paper will be free to access until May 5, 2020.
