(631m) Effect of Chistoan Molecular Weight On the Transport of Solutes Across a Model Pulmonary Epithelium

Due to its proximity to the bloodstream, oral inhalation (OI) of therapeutics is a viable non-invasive drug delivery strategy for targeting not only the diseases of the lung, but also for systemic delivery.  Characteristics such as its large surface area, thin cellular barrier, and low proteolytic activity makes the lung an attractive organ for administering therapeutics capable of successfully permeating into systemic circulation.  The intercellular tight junctions populating the pulmonary epithelia are among the several biological hindrances that need to be overcome in order to successfully transport relevant therapeutic moieties.  A strategy that has been widely employed for opening the tight junctions is the use of permeation enhancers.  One such permeation enhancer that has been successful shown to modulate the tight junctional properties of pulmonary epithelium is high molecular weight Chitosan (CS).  CS is a biocompatible, biodegradable polysaccharide that typically exhibits low cytotoxicity.

Several previous studies have focused on the permeation enhancement effects of CS at high molecular weights, and have concluded that CS was able to considerably enhance the transport of macromolecules across pulmonary epithelia.  Here, we discuss the permeation effects of both low and high MW CS on the transport across a pulmonary epithelium, Calu-3.  CS was depolymerized to different MWs.  Calu-3 cells were cultured on Transwell® inserts under an air-interface, grown to confluence and characterized.  The transport of solutes was evaluated in presence of CS with different MWs.

Keywords: Pulmonary drug delivery; Calu-3; permeation enhancement; transport of therapeutics