Some aspects of the technology for liposomal medicinal preparations

Abstract

For the last two decades we have been engaged in work on many fronts to create new drugs and diagnostic preparations based on phospho-and glycolipids. These works have included extensive investigations in three directions:(1) Search for raw material sources and development of commercial technologies for the isolation of high-purity useful fractions and individual phospho-and glycolipids of various types.(2) Study of the biological activity of lipids, in connection with their structures and physicochemical characteristics, and the design of drugs and diagnostic preparations based on these lipids with an allowance for the established relationships.(3) Development of optimum technological schemes for the production of liposomal preparations for medicinal purposes. [1 -8].The results of investigations in the first two directions have been reported previously [5 -12]. This paper deals with some technological aspects of the production of liposolnes loaded with drug preparations [I, 2, 13 -15].The process of liposome formation includes the following sequence of necessary stages: (i) preparation of lipid films from high-purity lipids oxidized to a minimum extent; (ii) emulsification of the lipid in a buffer solution or a solvent containing substances to be included in liposomes; (iii) formation of liposomes by conventional methods; (iv) separation of residual substances not encapsulated in liposomes; (v) clarification and sterilization of the liposomal preparation; (vi) pouring preparations into storage containers; (vii) freezing, lyophilization, and hermetization of preparations in an inert gas atmosphere; (viii) storage under preset conditions with periodic quality control [1,2,13]. It must be noted that According to our experience, the standardization and quality control of medicinal liposomal preparations must inelude determination of the following parameters: dimensions of liposomes; sterility, pyrogenicity, and toxicity of preparations; ratio (quantitative) of the lipid and drug components forming a given liposomal preparation; pH of the liposomal system; presence of stabilizing agents. The process of production and storage of liposomal preparations must also include periodic monitoring of the oxidation state and analysis for the possible appearance of lipid peroxidation products [16,17].According to the above scheme, the initial technological stages consist in obtaining a lipid film by dissolving a given lipid or lipid mixture in an appropriate organic solvent at a temperature not exceeding 33 _+ 2~ followed by removal of the solvent in vacuum. A hydrophobic biologically active compound (drug component), intended for the encapsulation in liposomes, is also dissolved in an appropriate organic solvent and lrfixed with the lipid solution. Upon the evaporation of solvents in vacuum, the lipid film containing the drug component is suspended in a buffer solution so as to obtain multilayer vesicles. During the suspensiong stage, the temperature usually is maintained above that of the phase transition in the lipid system ...