INFLUENCE OF FORMULATION FACTORS ON THE EFFICIENCY OF PASSIVE LOADING OF GEMCITABINE INTO LIPOSOMES

One of the promising approaches to eliminate the disadvantages of gemcitabine chemotherapy is its encapsulation in the liposomal delivery system. However, loading gemcitabine into liposomes is fraught with a number of difficulties, which requires rational formulation selection and optimization of the conditions of the production process. This study is devoted to studying the influence of technological factors of formulation on the effectiveness of passive loading of gemcitabine into liposomes. A thin-film method was used to obtain gemcitabine liposomes. The chloroform lipid solution was evaporated on a rotary evaporator to form a film, which was dried at low pressure and then hydrated with an aqueous gemcitabine solution. The resulting liposomal dispersion was extruded by passing through Nuclepore polycarbonate filters with a pore diameter of 0.4 and 0.2 microns. The concentration of the drug in the dispersion was determined by spectrophotometry using a standard sample at a wavelength of (268±2) nm. Gel filtration method using NAP-5 columns filled with sephadex G-25 was used to purify liposomal dispersion from non-activated gemcitabine. As a result, 20 model liposomal compositions were obtained, differing in qualitative and quantitative composition. By comparing the effectiveness of passive gemcitabine loading, the effect of the following potentially critical formulation parameters was studied: total lipid concentration, drug concentration, cholesterol and pegylated lipid content, phospholipid type (origin, degree of saturation, length of the hydrocarbon chain, charge). It has been shown that with an increase in lipid concentration, there is an increase in the efficiency of drug loading. At the same time, cholesterol and pegylated lipid, depending on the type of structurally forming phospholipid, can contribute to both an increase and decrease in the level of encapsulation. The properties of the structure-forming phospholipid have a significant effect on the efficiency of gemcitabine loading. The maximum switching efficiency (over 80%) and loading capacity (over 3%mas) is achieved when using compositions based on saturated phospholipids, characterized by a high phase transition temperature. Thus, the effect of liposomal composition on the effectiveness of gemcitabine encapsulation was studied. The data obtained can be used as a basis for the development of a liposomal dosage form of gemcitabine.