Efficacy of liposomal dosage forms and hyperosmolar salines in experimental pharmacotherapy of acute lung injury

Abstract

Introduction: Hypertonic sodium chloride solutions and liposomal drugs with pulmotropic effect are of great interest for the treatment of acute lung injury (ALI). The results of the studies on the efficacy of hypertonic solutions and liposomes in ALI treatment are currently controversial. Materials and methods: For the experiment, liposomes with dexamethasone, N-acetylcysteine (NAC), aprotinin and dye Cyanine-7 (Cy-7) were obtained. A liposome analysis was performed by means of spectrophotometry. ALI was modeled in rats by the administration of the damaging agents into the trachea. The experimental agents were injected once intravenously after the modeling of ALI. For experimental therapy used liposomal agents, 7.5% hypertonic saline (HS) and HyperHAES solutions in the respective groups. The efficacy of the therapy was assessed by the survival of animals, functional indicators of the cardiovascular and respiratory systems, and by the lung-body ratio. The biodistribution of liposomes after intravenous administration was investigated in mice through using a fluorescent dye Cy-7. The biodistribution of liposomes with Cy-7 was assessed using bioimaging according to the fluorescence intensity of internal organs (lungs, liver, and kidneys) and blood, expressed as dye concentration according to the calibration dependence of dye concentrarion on fluorescence intensity. Results and discussion: All the studied liposomal drugs were effective for the pharmacological correction of ALI. Hypertonic solutions, unlike liposomal drugs, were less likely to prevent the development of pulmonary edema. All the studied therapeutic agents increased the survival rate of the laboratory animals with ALI. The most effective experimental agent was liposomal dexamethasone. The use of drugs in form of simple liposomes with average diameter of 350 nm provided for a higher concentration of the drug in the lungs within the first 40 minutes after intravenous administration. Conclusion: Intravenous administration of liposomal forms is promising for the pharmacotherapy of acute lung injury.