Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3-Gallate: An In-Silico/Experimental Approach

Abstract

As a part of research project aimed to optimize antioxidant delivery, here we studied the influence of both salts and lipid matrix composition on the interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we combined in silico and experimental methods to study the ability of neutral and anionic vesicles to encapsulate EGCG in the presence of Ca2+ and Mg2+ divalent salts. Experimental and in silico results show a very high correlation, thus confirming the efficiency of the developed methodology. In particular, we found out that the presence of calcium ions hinders the insertion of EGCG in the liposome bilayer in both neutral and anionic systems. On the contrary, the presence of MgCl2 improves the insertion degree of EGCG molecules respect to the liposomes without divalent salts. The best and most efficient salt concentration is that corresponding to a 5:1 molar ratio between Mg2+ and EGCG, in both neutral and anionic vesicles. Concerning the lipid matrix composition, the anionic one results in better promotion of the catechin insertion within the bilayer since experimentally we achieved 100% EGCG encapsulation in the lipid carrier in the presence of a 5:1 molar ratio of magnesium. Thus, the combination of this anionic liposomal formulation with magnesium chloride, avoids time-consuming separation steps of unentrapped active principle and appears particularly suitable for EGCG delivery applications.

Conformational Insight on WT- and Mutated-EGFR Receptor Activation and Inhibition by Epigallocatechin-3-Gallate: Over a Rational Basis for the Design of Selective Non-Small-Cell Lung Anticancer Agents

“…Then, a 100 ns-long dynamic simulation was run for each system, implementing an accurate leapfrog algorithm or interacting Newton's equations of motion with a time step of 0.002 ps. This already validated MD protocol [55,56] was used for wild type, T790M/L858R and ELREA Deletion EGFR forms, while the analysis of the simulations' trajectories was performed by means of the VMD [57] and CHIMERA software [58].…”

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

“…EGCG beneficial effects are however counteracted by its poor membrane permeability, rapid metabolism and chemical instability in physiological environment [10,11]. The stabilization of EGCG can be obtained by different approaches including the employment of reducing agents, structural modification and/or drug delivery systems [12][13][14]. Among these, the application of derivatization strategies designed to increase the molecule hydrophobicity and the interaction with cellular membrane [15][16][17][18][19][20] is considered as a feasible approach to improve the activity of bioactive molecules.…”

Synthesis, Characterization and Antioxidant Properties of a New Lipophilic Derivative of Edaravone

“…This process results in the alteration of membrane fluidity and permeability, in the inactivation of membrane-bound enzymes and receptors, and in a general loss of the membrane functionality. Membrane-targeting antioxidants could counteract or prevent the LPO; [12] there is, therefore, an increasing interest toward strategies aiming to potentiate the interaction between antioxidants and lipid systems [6,13,14,15]. In order to obtain an EdV analogue possessing these characteristics, in this study we synthesized a lipophilic derivative, alkylated at position (4) of the pyrazolone ring with a C-18 hydrocarbon chain.…”