Yue Hu a,b,c, Yunhua Sheng c,e, Xiaoli Ji c,e, Ping Liu c,e, Liming Tang c,e, Gang Chen a,Guiliang Chen b,d,
a School of Pharmacy, Fudan University, Shanghai, China
b China State Institute of Pharmaceutical Industry, Shanghai, China
c Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai, China
d Shanghai Center for Drug Evaluation and Inspection, Shanghai, China
e NMPA Key Laboratory for Quality Analysis of Chemical Drug Preparations, Shanghai, China
In this study, the ALICE-CLOUD system was used as an easy-to-use and dosimetrically accurate ALI system for efficient delivery of the curcumin aerosol to the cells. It has been used to assess not only the respiratory effect of nanoparticles and chemicals after single or repeated exposure, but also the biokinetics of aerosolized drugs. Conventional ALI systems were mainly developed for toxicity study of inhaled substances. Compared with other systems, the ALICE-CLOUD system is not only technically simpler, easier to handle, but also has higher drug delivery efficiency and shorter exposure time. The short exposure time of the ALICE-CLOUD system was similar to the actual administration pattern of the inhaled drugs, which is suitable for preclinical development of aerosolized drugs and cellular response mechanisms for inhalation therapy.
Background: Inhalation of aerosolized drugs is a promising entry route for rapid and non-invasive therapeutics delivery to the lung. Curcumin exhibits potent anti-inflammatory properties, which are effective for use in lung diseases. The anti-inflammatory properties of curcumin have been widely studied in vitro with cells cultured in submerged conditions, however, the effectiveness using air-liquid interface (ALI) exposure is currently unknown.
Methods: The anti-inflammatory effect of curcumin under both ALI and submerged conditions was investigated in the present study. Lipopolysaccharide (LPS) stimulated A549 cells were exposed to curcumin under ALI (10–100 μM) using a dose-controlled air-liquid interface cell exposure (ALICE)-CLOUD system and submerged cell culture conditions (1–20 μM). The expression of pro-inflammatory cytokines (interleukin (IL)-6, IL-8), cell viability and cytotoxicity were studied for each exposure scenario. The cellular uptake behaviour of curcumin was studied with an equipotent cell-based dose (200 pmol/106 cell) at various time points up to 24 h.
Results: The ALI delivery profile proved to be rapid, efficient and reproducible. For the doses studied, no significant effect on cell viability and cytotoxicity were observed. ALI exposure of curcumin was more effective in reducing pro-inflammatory cytokines expression in lung epithelial cells compared with submerged cell cultures. Furthermore, rapid cellular uptake and higher intracellular doses were achieved by ALI conditions. Conclusions: The ALICE-CLOUD system combined with lung epithelial cells cultured under ALI conditions offers a reliable and relevant in vitro method for preclinical aerosolized drug screening. Curcumin might be a promising anti-inflammatory candidate drug for inhalation therapy of lung diseases.