Abstract
Abstract The objective of the present study was to establish the individual and combined chemopreventive potential of a widely used non-steroidal anti-inflammatory drug, ibuprofen (IBU), encapsulated in solid lipid nanoparticles (SLNs) for the chemoprevention of pancreatic cancer. The synergistic effect of combination of IBU with sulforaphane (SFN) was also evaluated. Cell viability studies were conducted followed by colony formation and NF-κB DNA binding assays. The IC50 concentration of free IBU in human pancreatic cancer cells Panc-1 and MIA PaCa-2 were 1.25mM and 1.26 mM, respectively. SLN optimization study of IBU revealed stearic acid (1:2 drug to lipid ratio) formulated with Poloxamer 188 to be the most efficacious in cell viability study. Upon encapsulation in SLNs, IC50 concentration of IBU-SLN was 113.8 μM and 122.6 μM for Panc-1 and MIA PACa-2 cells respectively, reflecting a 10-fold reduction compared to free IBU. Combinations of low doses of free IBU (250 μM) and SFN (5 μM) reduced cell viability by ∼55% (P<0.01), whereas a lower dose of encapsulated IBU-SLN (62.5 μM) and free SFN (5 μM) reduced cell viability by ∼80% (P<0.001) for both Panc-1 and MIA PaCa-2 cells. These results reflect 4-fold reduction in IBU-SLN dose in combination compared to free IBU. Moreover, IBU-SLN and free SFN combination reduced number of colonies by ∼50% (P<0.01). Further, IBU-SLN and SFN combinations showed down-regulation of DNA binding activity of the p50 subunit of NF-κB. In conclusion, these preliminary results demonstrate the potential of IBU as a chemopreventive agent against pancreatic cancer. Furthermore, when encapsulated in nanotechnology-based SLN delivery systems and delivered in combination with SFN provide evidence of a promising approach for pancreatic cancer prevention and therapy. Citation Format: Arvind Thakkar, Sushma Chenreddy, Jeffrey Wang, Sunil Prabhu. Evaluation of Ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2824. doi:10.1158/1538-7445.AM2015-2824
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