title: Chemoprevention of pancreatic cancer using solid-lipid nanoparticulate             delivery of a novel aspirin, curcumin and sulforaphane drug combination regimen.
abstract: Pancreatic cancer is the fourth largest cause of cancer deaths in the Unites States and the prognosis is grim with <5% survival chances upon diagnosis. The objective of this study was to assess the combined chemopreventive effect of solid lipid nanoparticle (SLN) encapsulated drugs aspirin (ASP), curcumin (CUR) and free sulforaphane (SFN) for the chemoprevention of pancreatic cancer. Experiments were carried out (1) to evaluate the feasibility of encapsulation of these chemopreventive agents within solid lipid systems and (2) to measure the synergistic effects of a combination of ASP with CUR in SLNs mixed with free SFN against cell proliferation and apoptosis in pancreatic cancer cells, MIA PaCa-2 and Panc-1. The SLNs were prepared using a modified solvent evaporation technique and were characterized for particle sizing, encapsulation efficiency and drug release. ASP and CUR SLNs were formulated within the particle size range of 150‑250 nm and were found to have an encapsulation efficiency of 85 and 69%, respectively. Sustained release of drugs over a 96 h period from SLNs was observed. The SLNs were stable over a 3-month storage period at room temperature. Cell viability studies demonstrated that combinations of low doses of ASP SLN (25 µM), CUR SLN (2.5 µM) and free SFN (5 µM) significantly reduced cell viability by 43.6 and 48.49% in MIAPaca-2 and Panc-1 cell lines, respectively. Furthermore, increased apoptosis of 61.3 and 60.37% was found in MIA Paca-2 and Panc-1 cell lines, respectively, in comparison to the individual doses administered. Synergistic effects were demonstrated using MTS and apoptosis assays. Thus, this study successfully demonstrated the feasibility of using a solid lipid nanoparticulate system for the first time to deliver this novel combination chemoprevention regimen, providing valuable evidence for the usability of nanotechnology-based drug regimens towards pancreatic cancer chemoprevention.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western                     University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Dhruvitkumar
authors.initials: D
authors.lastname: Sutaria
authors.forename: Balagangadhar Karthik
authors.initials: BK
authors.lastname: Grandhi
authors.forename: Arvind
authors.initials: A
authors.lastname: Thakkar
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wang
authors.forename: Sunil
authors.initials: S
authors.lastname: Prabhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018890:Chemoprevention; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004338:Drug Combinations; D004355:Drug Stability; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D017879:Isothiocyanates; D008055:Lipids / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry*; D058726:Nanoconjugates / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010316:Particle Size; D013454:Sulfoxides; D013861:Thiocyanates / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D017879:Isothiocyanates; D008055:Lipids; D053769:Nanocapsules; D058726:Nanoconjugates; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane; D003474:Curcumin; D001241:Aspirin