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January 5, 2007

Interaction between  Pseudomonas aeruginosa and cyclodextrin treated lung epithelial cells: implications in cyclodextrin assisted drug delivery through the lungs

Emmanuel Dotsey, Nilesh Patel, PhD., Ben Forbes, PhD., Gary Martin, PhD.

Pharmaceutical Sciences Research Division, King’s College London, UK

Abstract

            To identify the ideal cyclodextrin for use as a drug delivery tool for the transport of a hydrophobic drug candidate through the lungs, we studied two cyclodextrins, namely Randomly methylated β-cyclodextrin (RAMEB-CD) and Hydroxypropyl-β-cyclodextrin (HPβ-CD). We used Calu-3 lung epithelial cells as a model for human lung epithelial cells. Trans-epithelial electrical resistance (TER) readings of cells pre-treated with RAMEB-CD showed RAMEB-CD toxicity at 50 mM. On the other hand, cells treated with HPβ-CD were able to recover their TER within 28 h and no toxicity was observed at 50 mM. We also studied the interaction between the environmental bacteria Pseudomonas aeruginosa (PsA) and cyclodextrin-treated lung epithelial cells. We hypothesized that contact with bacterial proteins will trigger a host response that will lead to a change in the expression of the tight junction protein ZO-1 compared to the control leading to a change in the TER. It is know that the presence of the tight junction protein ZO-1 confers junctional integrity to Calu-3 cells. The fact that the PsA treated cell layers consistently presented a higher TER and a slower TER drop rate compared to the control as indicated by our initial results led to the belief that the presence of the PsA may have caused a host response which resulted in the up-regulation of ZO-1 protein. To confirm these conclusions, further work is required to assay for the ZO-1 protein in the control and the cells exposed to the PsA.

 


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