(601e) Effect of Chitosan Molar Mass and Graft Chemistry On the Transport of Therapeutics Across a Model Airway Epithelium

Oral inhalation (OI) is not only the most sensible rout for the regional delivery of therapeutics to the lungs, but it is also a viable non-invasive route for the delivery of therapeutics to the systemic circulation.  The lungs are an attractive pathway to the bloodstream as they have a large surface area, consist of a thin cellular barrier, and have lower proteolytic activity compared to those observed in traditional delivery routes.  The cellular tight junctions populating the pulmonary epithelia highly modulate the transport into systemic circulation.  Permeation enhancers such as chitosan (CS), a biodegradable polysaccharide that typically exhibits low cytotoxicity, may be potentially employed for opening the tight junctions, and thus for modulating the transport of therapeutics across the pulmonary epithelium.

In this work we discuss the effect of CS molar mass and graft chemistries on the transport of various model solutes, including a small hydrophilic molecule, a model protein, and a hydrophobic therapeutic across polarized Calu-3 monolayers, an established in vitro model of the human airway epithelium.  The relevance of this work stems from the fact that the ability to modulate the transport of therapeutics across the pulmonary epithelium may improve the market share of OI formulations in the overall drug delivery market.