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

评估使用可吸入脂质体地塞米松的细胞毒性和临床前安全性

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作者:O A Kulikov, D V Yunina, V P Ageev, V I Shlyapkina, I S Avdyushkina, I A Akmaeva, A V Zaborovsky, L A Tararina, S V Tsaregorodtsev, N A Pyataev

Abstract

A liposomal form of dexamethasone was obtained. Liposomal vesicles were formed. The efficiency of incorporating dexamethasone into the liposomes was 99.7%. The cytotoxicity of the obtained liposomes was studied on a culture of human lung fibroblast cells using the MTT assay. The toxicity of liposomal dexamethasone was less than that of dexamethasone solution after a 24-h incubation. The half-maximum inhibitory concentration (IC50) was not achieved after 24 h when exposed to liposomal dexamethasone whereas IC50 was 27.5 mg/mL for lecithin (empty liposomes) and 177 µg/mL for dexamethasone solution. The toxicity of liposomal dexamethasone increased much more than that of dexamethasone solution after 48 h of incubation with IC50 values of 36 and 156 µg/mL, respectively. Thus, the liposomal form of dexamethasone has a latent period for implementation of the cytostatic (antiproliferative) action. Experiments on laboratory white rats of both sexes revealed that the inhalation use of liposomal dexamethasone insignificantly changed the functional parameters of their respiratory and cardiovascular systems. The study results could be used for conducting clinical trials.

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