Experimental approaches to modelling the enzymatic function of biological membranes are discussed. Emphasis is given to pseudohomogeneous systems such as proteolipid complexes and enzymes in organic solvents; the latter are solubilized with phospholipids or synthetic surfactants. Methods for producing and studying such micellar systems are considered. The key research problems of micellar enzymology are formulated and its relation to enzyme membranology is discussed. Finally, the new potentialities are noted of applied enzymology (biotechnology) offered by application of a colloidal solution of water in organic solvents as a microheterogeneous medium for enzymatic reactions.Until now the development of molecular enzymology has been mainly directed to studying free enzymes [l -41. In other words, the most valuable experiments aimed at elucidating the structure of catalytic centers and the physico-chemical mechanisms of biocatalysis were successful only with the enzymes isolated from the living cells in quite a pure form. However, such 'pure' experiments, as was noted time and again [5], naturally raise the question as to whether the enzyme properties observed in vitro can be correlated adequately with the conditions of its functioning in vivo. Such a doubt is quite equitable since it became clear [6 -91 that the subcellular structure and the compartmentalization of enzymes play the most important role in metabolism regulation.Thus, the essence of the contradiction is that in vitro studies of enzymes are usually conducted in water (buffer). However, in the living cell, enzymes mostly act on or near the 'water/ organic medium' interface. For instance, many enzymes, if not the majority, are located on the surface of biological membranes or inside them [lo-161. Other enzymes function in mobile complexes with macromolecular components of the cell, e.g. with proteins or polysaccharides [14 -161. Generally speaking, the boundary between 'bound' and 'diffusion-free' enzymes is rather conventional, and such a classification is more methodical (depending on the ease of the enzyme isolation) than functional (the enzyme localization in the cell) [16]. The problem is that many of the enzymes bind to the membrane surface loosely and the degree of their binding depends on the concentration of metabolites [14-191. The physiological state of the cell determines not only the adsorption of some enzymes but their possible translocation through membranes [20,21]. In the adsorbed state in vivo (on the enterocyte brushborder) extracellular enzymes were found as well, such as proteases of the digestive tract, namely trypsin and a-chymotrypsin [22, 231, which up to now have remained model subjects of the classical 'in-water' enzymology.Finally, a few words about the medium in which diffusionfree enzymes function in the cell (for a review see [24]). It is not very clear why macromolecules (immunoglobulins and albumin) injected into the living cell diffuse so slowly (as in a 60% sucrose solution) [25]. The comparison of the diffusion rat...

Drug nanoformulations hold remarkable promise for the efficient delivery of therapeutics to a disease site. Unfortunately, artificial nanocarriers, mostly liposomes and polymeric nanoparticles, show limited applications due to the unfavorable pharmacokinetics and rapid clearance from the blood circulation by the reticuloendothelial system (RES). Besides, many of them have high cytotoxicity, low biodegradability, and the inability to cross biological barriers, including the blood brain barrier. Extracellular vesicles (EVs) are novel candidates for drug delivery systems with high bioavailability, exceptional biocompatibility, and low immunogenicity. They provide a means for intercellular communication and the transmission of bioactive compounds to targeted tissues, cells, and organs. These features have made them increasingly attractive as a therapeutic platform in recent years. However, there are many obstacles to designing EV-based therapeutics. In this review, we will outline the main hurdles and limitations for therapeutic and clinical applications of drug loaded EV formulations and describe various attempts to solve these problems.

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