Liposomal Formulation Reduces Transport and Cell Uptake of Colistin in Human Lung Epithelial Calu-3 Cell and 3D Human Lung Primary Tissue Models

Abstract

Respiratory tract infections caused by multi-drug-resistant (MDR) bacteria have been a severe risk to human health. Colistin is often used to treat the MDR Gram-negative bacterial infections as a last-line therapy. Inhaled colistin can achieve a high concentration in the lung but none of aerosolized colistin products has been approved in the USA. Liposome has been reported as an advantageous formulation strategy for antibiotics due to its controlled release profile and biocompatibility. We have developed colistin liposomal formulations in our previous study. In the present study, the cellular uptake and transport of colistin in colistin liposomes were examined in two human lung epithelium in vitro models, Calu-3 monolayer and EpiAirway 3D tissue models. In both models, cellular uptake (p < 0.05) and cellular transport (p < 0.01) of colistin were significantly reduced by the colistin liposome compared to the colistin solution. Our findings indicate that inhaled colistin liposomes could be a promising treatment for extracellular bacterial lung infections caused by MDR Pseudomonas aeruginosa (P. aeruginosa).

Keywords: 3D human lung epithelial tissue model; Calu-3 cell; colistin; liposome; pulmonary delivery.

Figure 1.

In vitro colistin release profile of the liposomal formulation in HBSS at 37°C (mean ± SD, n = 3).

Figure 2.

TEER value before and after the transport study (mean ± SD, n = 3). A) TEER value of Calu-3. B) TEER value of EpiAirway 3D tissue.

Figure 3.

Colistin (col) uptake and transport in Calu-3 monolayer or EpiAirway 3D tissue model (mean ± SD, n = 3, * p<0.05, ** p<0.01, assessed by Unpaired t test using GraphPad Prism Version 9.0). A) Cellular uptake in Calu-3 monolayer. B) Cellular uptake in the EpiAirway 3D tissues. C) Remaining drug in apical chamber of Calu-3 monolayer. D) Remaining drug in the apical chamber of EpiAirway 3D tissue.