Abstract 2238: Self-microemulsifying drug delivery systems (SMEDDS) containing novel compounds for the chemoprevention of pancreatic cancer

Abstract

Abstract Pancreatic cancer (PC) is the fourth leading cause of deaths in the United States, claiming approximately 43,000 lives every year. Existing trends suggest that it will be the second cause of death after lung cancer within the next 20 years. With mortality rates remaining high even after decades of research, scientists are now turning to develop chemopreventive strategies that may stop or delay the initiation and progression of the disease. Our study reports the chemoprevention potential of (1) a free drug combination of H1-receptor antagonist drug with Sulforaphane (SFN), a neutraceutical compound derived from broccoli and (2) lipid nanocarriers of H1-receptor antagonist drug (SP1 SMEDDS; formulation patent pending) with free SFN when administered at low doses in human pancreatic cancer cell lines (MIA PaCa-2 and Panc-1). IC50 concentrations were calculated for various treatment groups using MTS viability assay in accordance with published protocol, using 96-well microplates and incubation time of 72 h. The free drug combination revealed almost 70-fold and 20-fold enhancement in chemoprevention efficacy (based decrease in cancer cell viability) as compared to controls. Interestingly, the free drug combination (at 5µM) showed ~55 % (p<0.001) inhibition in cell lines whereas no measurable response was observed with individual free drug treatments at the same concentration. This confirmed the synergistic chemoprevention potential of the free drug combination. SP1 SMEDDS were optimized for particle size, encapsulation efficiency and chemoprevention efficacy. SP1 SMEDDS (10µM) by itself exhibited 54% (p<0.001) cell line inhibition whereas no measurable response was observed with free drug at that same concentration, confirming the potential of lipid nanocarriers in enhancing the chemoprevention activity. Moreover, the SP1 SMEDDS in combination with free SFN demonstrated synergistic activity with 500-fold, 140-fold and 7-fold enhancement in chemoprevention potential as compared to the free HI-receptor antagonist, SFN and the free drug combination, respectively. In conclusion, a novel lipid formulation of an H1-receptor antagonist in combination with free SFN was invented (provisional patent applied) to successfully elicit PC chemoprevention. Future studies will look into the efficacy of this novel formulation in in vivo PC models. Citation Format: Preshita Desai, Arvind Thakkar, Jeffrey Wang, Sunil Prabhu. Self-microemulsifying drug delivery systems (SMEDDS) containing novel compounds for the chemoprevention of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2238.