Membrane\nComposition Allows the Optimization of Berberine\nEncapsulation in Liposomes

Berberine (BBR) is a natural molecule with noteworthy\npharmacological\nproperties, including the prevention of antibiotic resistance in Gram-negative\nbacteria. However, its oral bioavailability is poor, thus resulting\nin an impaired absorption and efficacy in humans. In combination with\nother drugs, liposomes have been shown to enhance the availability\nof the drug, representing a smart delivery system to target tissues\nand reduce negative side effects. To date, there is a lack of studies\non BBR and liposomes that enable the rationalization and molecular-based\ndesign of such formulations for future use in humans. In this work,\nthe encapsulation of BBR into liposomes is proposed to overcome current\nlimitations using a combination of experimental and computational\nassays to rationalize the membrane composition of liposomes that maximizes\nBBR encapsulation. First, the encapsulation efficiency was measured\nfor several membrane compositions, revealing that it is enhanced by\ncholesteryl hemisuccinate and, to a lesser extent, by cholesterol.\nThe physical basis of the BBR encapsulation efficiency and permeability\nwas clarified using molecular dynamics simulation: using the lipid\ncomposition, one can tune the capability of membranes to attract,\ni.e., to adsorb, the molecules onto their surface. Overall, these\nfindings suggest a rational strategy to maximize the encapsulation\nefficiency of liposomes by using negatively charged lipids, thus representing\nthe basis for designing delivery systems for BBR, useful to treat,\ne.g., antibiotic resistance.