Features of the Technology of Liposomal Formulation of a Analogue Hypothalamic Hormone Somatostatin

Abstract

Background. In connection with the prospect of the use of an analog of the hypothalamic hormone somatostatin synthesized by the laboratory of chemical synthesis Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin Russian Cancer Research Center» and showed a high anti-tumor activity as a drug arises a need to establish an optimal technology of its receipt. In preliminary studies in a modelformulation for an analog of the hypothalamic hormone somatostatin selected liposome technological process of which has a series of specific steps comprising. Objective. Development of technology for obtaining liposomal formulation hypothalamic hormone somatostatin analogue. Materials and methods. Liposomes analog of the hypothalamic hormone somatostatin obtained by method Bengema in modification for hydrophobic substances. To reduce the diameter of the liposome are used methods extrusion, homogenization and ultrasonic. Analysis of the size of the liposomes was performed by correlation spectroscopy light scattering using nanosizer. The pH of the liposomal dispersion was determined by potentiometry. The quantitative content of the drug substance was determined by spectrophotometry using a standard sample with X (282 ± 3) nm and an alcoholic solution of empty liposomes as a reference solution. Amount of incorporated drug was calculated as the ratio of the concentration of drug in the liposome dispersion after filtration to the concentration of drug in the dispersion after preparation. Results and Conclusion. The hydrophobic nature of the substance causes an analog of the hypothalamic hormone somatostatin technological features of obtaining liposomal formulation. Since the step of forming a film of the lipid substance is dissolved in an organic solvent together with lipids, film is hydrated by a solution of cryoprotectant. Grinding liposomes an analog of the hypothalamic hormone somatostatin appropriate to be carried out using homogenization or extrusion methods, due to the high efficiency of these methods, the preservation stability of the liposomes and a high percentage of inclusion an analog of the hypothalamic hormone somatostatin, included in the liposomal bilayer. At the stage of separating the non-inclusion of substance an analog of the hypothalamic hormone somatostatin due to the insolubility of the substance in the water, you can use the filtering method, without the need for complicated procedures gel filtration, dialysis, etc. Furthermore the process of separating a substance not included can be combined with the sterilization of the liposome dispersion by selecting a particular filter material.

Selection of the Composition of a Liposomal Dosage Form of a Russian Somatostatin Analogue With Antitumor Activity

“…Using these components, we derived the model of the liposomal pharmaceutical dosage form with molar ratios of cyphetrylin/EPC at 1:70.0 and those of EPC/cholesterol/PEG-DSPE at 1:0.2:0.003. The created cyphetrylin liposomal dispersion has 98% drug encapsulation rate and with 168±6 nm vesicle size [16].…”

“…"Empty" liposomes were generated in the same way as those with an active substance, but without adding cyphetrylin to the drug components organic solution. Using cyphetrylin, SPC, cholesterol, and PEG-DSPE, we generated and tested 15 model compositions of cyphetrylin in the liposomal pharmaceutical dosage form with different components molar ratios (table 1) [16]. Measure the test solution's optical density in trays with 10 mm optical layer "thickness", in maximum absorption compared with the comparison solution.…”

“…А and А0-optical densities of the liposomal sample solutions and cyphetrylin RS, respectively; а0-weight of cyphetrylin RS, mg; 2volume of cyphetrylin liposomal sample, ml [16].…”

“…Сe-cyphetrylin concentration in dispersion after extrusion, mg/ml; Сh-cyphetrylin concentration in dispersion after hydration, mg/ml [16].…”