Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention
Menée in vitro, cette étude évalue l'efficacité chimiopréventive de l'ibuprofène, encapsulé dans des nanoparticules lipidiques solides, et du sulforaphane dans le cancer du pancréas
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 IBU SLNs were optimized using various lipids (Stearic acid, Compritol 888 ATO and Tripalmitin) and surfactants (Poloxamer 188, Tween-80). The synergistic effect of combination of IBU with sulforaphane (SFN) was also evaluated. Cell viability studies were conducted followed by colony formation and NF-kappaB DNA binding assays. The IC50 concentration of free IBU in human pancreatic cancer Panc-1 and MIA PaCa-2 cells were 1.25 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 and 122.6 microM 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 microM) and SFN (5 microM) reduced cell viability by ~55% (P<0.01), whereas a lower dose of encapsulated IBU-SLN (62.5 microM) and free SFN (5 microM) 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-kappaB. 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.