Абстрактный

Resveratrol �?²-Cyclodextrin/Lecithin Complexes: A New Approach for Treatment of Hepatic Dysfunction

Gehan F Balata, Naser A ElSawy, Mohamad AS Abourehab, Nedaa Ali Karami, Abdualrhmain Bahowirth, Walaa Al Nemari, Mashael Al Daajani and Ferdous Mohammed Turkistani

Objective: The prevalence of liver diseases in Saudi Arabia is relatively high, and the mortality rates are significant. So, the aim of the study was to modify the physicochemical and hence biological characteristics of trans-resveratrol, a hepatoprotective agent, through the formation of ternary β-cyclodextrin/soybean lecithin complexes by solvent evaporation and freeze drying techniques using a 23-full factorial design methodology.

Methods: Solubility of resveratrol in presence of (0 M to 0.02 M) β-cyclodextrin with and without 0.5% lecithin was studied. The prepared complexes were evaluated by dissolution study, scanning electron microscopy, differential scanning calorimetry and x-ray powder diffractometry. The effect of β-cyclodextrin and soybean lecithin concentration and preparation method, independent variables, on the amount of resveratrol released after 10 min (Q₁₀) and dissolution efficiency after 60 min (DE₆₀), dependent variables, were studied using contour plot and interaction surface plot. Finally, the therapeutic effectiveness of the optimized resveratrol complex (F8) compared to a commercial silymarin product (Legalon)^© was investigated biochemically and histopathologically in rats after carbon tetrachloride (CCl₄)-induced hepatotoxicity.

Results: The results revealed that the addition of lecithin increased the complexation efficiency and the stability constant by about 3 folds. Physicochemical characterization using scanning electron microscopy, differential scanning calorimetry and x-ray powder diffractometry revealed resveratrol complexation within β-cyclodextrin cavity with reduction in drug crystallinity. The contour and interaction charts indicated that the method of complex preparation was the most important factor affecting dissolution performance of resveratrol from its complexes followed by lecithin concentration and then β-cyclodextrin concentration. The optimized resveratrol complex (resveratrol: β-cyclodextrin: lecithin, 1:2.5:0.5 w/w) had a pronounced therapeutic effect against hepatic damage when compared with the commercial silymarin product (Legalon)^©.

Conclusion: Ternary resveratrol complex with cyclodextrin and lecithin may be a good alternative medicine for treatment of liver damage.