Efficacy and Pharmacokinetic Considerations of Loratadine Nanoformulations and its Combinations for Pancreatic Cancer Chemoprevention

PurposePancreatic cancer (PC) is predicted to become the second leading cause of cancer associated deaths by 2020. Earlier, we confirmed the development and efficacy of our novel Loratadine Self-Microemulsifying-Drug-Delivery-System - Sulforaphane (LOR SMEDDS -SFN) nanoformulation in PC chemoprevention. In this report, we extend our studies to evaluate the PC chemoprevention efficacy of LOR SMEDDS - SFN.MethodsThe nanoformulation was subjected to in vitro colony formation assays, in vivo oral pharmacokinetics and stability studies.ResultsThe colony formation assay using Panc-1 PC cells demonstrated a survival fraction of 0.74 with LOR-SFN (p <0.001) which further reduced to 0.35 with LOR SMEDDS-SFN treatment (p <0.0001) confirming the synergistic chemoprevention efficacy of the nanoformulation. Further, the oral pharmacokinetic studies of LOR SMEDDS-SFN showed 4-fold and 9-fold increase in C-max (503.25.8 ng/mL) and oral bioavailability (20,274.8 +/- 3711.0 ng.h/mL) for LOR compared to LOR-SFN combination respectively assuring the enhanced performance by the SMEDDS. Additionally, the formulation exhibited statistically non-significant alteration in globule size, zeta potential, drug content and in vitro drug release during stability studies confirming its stability and pharmaceutical acceptability.Conclusion Our studies have demonstrated a potential of LOR SMEDDS-SFN nanoformulation as an effective PC chemoprevention strategy.