Résumé
The therapeutic potential of curcumin (Cur) is hampered by its poor aqueous solubility and low bioavailability.The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur.Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology,droplet size and zeta potential.The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur.Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur,as assessed by apoptosis and cell cycle studies.In siru single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur.Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.
Résumé
This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate. The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium. In vitro release was detected by a dialysis method in reverse. The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes. The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique. The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting. Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500. The MDZ was completely released in 10 h. A significant decrease in the formation of 1'-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed. A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250. This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.