The past two decades of research have proved unsuccessful in finding a viable treatment option for pancreatic cancer. As many cancer rates continue to decline, pancreatic cancer incidence and mortality is expected to increase going forward. Due to lack of suitable treatment modalities and <5% chances of survival upon diagnosis, an alternative approach lies in chemoprevention, using suitable agents that can inhibit or reverse the progression of this disease. Our group was the first to report a novel combinatorial approach of low concentrations of aspirin, curcumin and sulforaphane (ACS) administered via a nanotechnology-based oral drug delivery system using solid-lipid nanoparticles (SLNs). Results from these pilot studies, both in vitro and in vivo, showed significant synergistic decrease in cell viability, increased cell apoptosis and significant reducton in pancreatic intraepithelial neoplasms (PanINs) when using this novel approach. While these data appear to be promising for pancreatic cancer chemoprevention, many new questions remain unanswered. In this proposal, we are focused on further investigation of an ideal formulation strategy for long-term oral administration of ACS, using a second generation of SLNs conjugated with chitosan (c-SLN) for improved targeting of the pancreatic tissues. Additionally, we will look at toxicity profiles, pharmacokinetics and biodistribution in pancreatic tissue and ensure efficacy in a transgenic mouse model. Overall, based on our strong preliminary results and related publications, we believe the outcomes of this proposal will establish the groundwork to consider the ACS nano-regimen with c-SLNs as a viable approach for the chemoprevention of pancreatic cancer.
Use of novel combination regimens of aspirin, curcumin and sulforaphane delivered via a nanotechnology-based system will provide important information for future clinical applications of chemopreventive strategies against pancreatic cancer.
|Thakkar, Arvind; Desai, Preshita; Chenreddy, Sushma et al. (2018) Novel nano-drug combination therapeutic regimen demonstrates significant efficacy in the transgenic mouse model of pancreatic ductal adenocarcinoma. Am J Cancer Res 8:2005-2019|
|Ding, Baoyue; Wahid, Md Arif; Wang, Zhijun et al. (2017) Triptolide and celastrol loaded silk fibroin nanoparticles show synergistic effect against human pancreatic cancer cells. Nanoscale 9:11739-11753|
|Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid et al. (2016) Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice. Int J Nanomedicine 11:3265-76|