The objective of present work was to investigate permeability characteristics of an anticancer berberine, in presence and absence of bioenhancer quercetine on goat intestine using Franz diffusion cell. A 32 full factorial design approach was employed to investigate the effect of independent variables such as concentration of bioenhancer (X1) and pre-treatment time (X2) on dependent variable % cumulative drug release (% CDR) (Y) using Design Expert software. The effect of quercetine was examined at 3 different levels of pre-treatment time (30, 45 and 60 min) and at 3 different concentrations (2, 6 and 10 mg) on goat intestine. The apparent permeability (Papp), flux (J) and enhancement ratio (ER) were determined. Further, in vitro anticancer activity of optimized batch was performed on various cancer cell lines K562, A459 and Hela. During pre-treatment studies, it was observed that, increase in concentration of quercetine yielded positive effect on % CDR while increase in pre-treatment time by quercetine had detrimental effect on % CDR. When goat intestine was pre-treated for 30 min with 10 mg of quercetine, 90.91 ± 1.66% CDR was obtained while minimum value of 17.45 ± 2.12 % CDR was observed at 2 mg quercetine pre-treated for 60 min. In vitro anticancer activity of optimized batch demonstrated non-significant effect as compared to parent drug. It conclusion, quercetine could be successfully utilized as bioenhancer to improve ex vivo permeability of berberine which would be expected to improve its bioavailability and reduce the dose resulting in improved patient compliance.
Key words: Berberine; bioenhancer; quercetine; 32 full factorial design; ex-vivo permeability study; in- vitro anticancer activity
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