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

Abstract

Citation: Kulikov OA, Ageev VP, Marochkina EE, Dolgacheva IS, Minayeva OV, Inchina VI (2018) Efficacy of liposomal dosage forms and hyperosmolar salines in experimental pharmacotherapy of acute lung injury. Research Results in Pharmacology 5(2): 23-41. https://doi. AbstractIntroduction: 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.

Nanomedicines Targeting Respiratory Injuries for Pulmonary Disease Management

“…Results showed that liposomes with average diameter of 350 nm efficiently targeted the lungs after intravenous administration and the liposomal formulations were effective in pharmacological repairment of ALI. [ 106 ] Moreover, liposomes have also been proposed to enhance the bioavailability of drug after oral administration. Liposome‐encapsulated spironolactone (Lipo‐SP) was prepared for ALI treatment via oral administration, which resulted in enhanced SP bioavailability with therapeutic/preventive potential for ALI by modulating the inflammatory phenotypes of circulating monocytes/lung macrophages.…”

“…[ 117 ] The excellent safety of liposomal components makes them highly appealing for drug delivery to the lung tissues. [ 106 ]…”

“…[117] The excellent safety of liposomal components makes them highly appealing for drug delivery to the lung tissues. [106] GCs are widely used for inflammatory and autoimmune diseases because of strong anti-inflammatory and immunosuppressive effects, [118] nevertheless, GCs have a series of adverse effects, such as gastrointestinal bleeding, aggravation of infection, and leading to peptic ulcer, et al [119] High-dose of GC is usually required to achieve satisfactory therapeutic efficacy due to the whole-body distribution, which causes serious side effects. [120] In this case, as shown in Figure 5 The bioavailability of SP was enhanced and the lung pathology was ameliorated significantly.…”

Evaluation of Cellular Toxicity and Preclinical Safety of Using an Inhalable Liposomal form of Dexamethasone

“…Dexamethasone has been highly regarded around the world for the new COVID-19 coronavirus infection [8] as an agent for battling intoxication, inflammation, and sclerotic changes in the lungs [9]. A liposomal form of dexamethasone that was studied for intravenous administration in models of lung pathology is certainly interesting [10,11]. However, scientific research on inhalation liposomal glucocorticosteroids is exceedingly rare [12].…”