Introduction: The present study aimed to formulate and evaluate Berberine nanophytosomes. A 2-level factorial design with midpoints was selected for the design of experimentation. Further, it was extended to a central composite design. Materials & Methods: The ratio of drug: lipid and probe sonication time were the factors, and vesicle size, PDI & % Entrapment Efficiency (% EE) as responses. Molecular docking studies of the drug were performed on alpha-glucosidase with acarbose (3W37) protein. FTI-IR and solubility studies were conducted as preformulation studies. Berberine nanophytosomes were formulated and optimized by the Design of Experiments-based technique. In vitro drug release studies, SEM, TEM, in vitro antidiabetic activity, and safety studies on VERO cells were performed. The recent patents granted on Berberine nanoparticles were US 2023/0181547 A1, WO 2022/168124 A1, 202011054150, 202111011487, and 2625/CHE/2013. Results: The multiple linear regression analysis revealed that vesicle size increased upon increasing the ratio of Drug:soyalecithin & probe sonication, but at the midpoint level, the size reduced. At 3 min probe sonication, greater than 80% EE was observed, and at the midpoint level, greater than 90 % was observed, but upon increasing the time to 5 min, the % EE decreased. An optimum PDI value was observed at mid-point level, i.e, 0.5. ANOVA was used to identify a significant effect. The drug release studies revealed that at pH 6.8, almost 90% of the drug was released. The zeta potential value of the optimized formulation was found to be -7.1 mV, indicating stability. SEM and TEM studies indicated a spherical shape of the particles. Discussion: Berberine had a greater inhibiting effect on alpha-glucosidase enzyme with an IC50 of 206.1±0.49 μg/ml, whereas Berberine nanophytosomes exhibited extensive inhibition with an IC50 value of 118.5±0.26 μg/ml, almost a 1.74 times reduction in IC50 value. Finally, safety studies of formulated nano-preparation on VERO cells indicated safety. Conclusion: This study reports, for the first time, a statistically optimized (central composite designbased) Berberine soyalecithin nanophytosomal system that improves solubility, bioavailability, and enzyme inhibition efficacy while maintaining safety. Unlike previous patented formulations, this work combines experimental optimization, molecular docking, in vitro enzyme inhibition, and cytocompatibility validation, establishing a scientifically integrated approach toward Berberine-based antidiabetic nutraceutical development.
Shivarani et al. (Fri,) studied this question.