(143a) Transport Modulation of Nanocarriers Across the Pulmonary Epithelium: Potential Strategy for the Local and Systemic Delivery of Drugs to and Through the Lungs

While it has long been recognized as an attractive non-invasive mode for delivering therapeutics to treat regional disorders, the potential for administering medicaments to the lungs via oral inhalation (OI) for targeting systemic ailments is rapidly gaining momentum due to the proximity of the organ to the bloodstream, low proteolytic activity and a large surface area.  Incorporating versatile delivery agents like polymeric nanocarriers (PNCs) into OI regimen can greatly enhance the applicability of such therapies for regional delivery, as PNCs have several advantages that include ease in cellular internalization, specificity in targeting and sustained release of encapsulated therapeutics.  The versatility of PNCs can be further enhanced by tailoring their surface properties, which may potentially assist in overcoming cellular barriers and aid in the modulation of transport of drug molecules.

In this work a series of surface-modified dendrimer nanocarriers (DNCs) were synthesized, characterized and their interaction with a model pulmonary epithelium was investigated.  Calu-3 cell monolayers were grown to confluence under an air-interface culture (AIC) and were characterized.  The transport and uptake of DNCs across these monolayers was studied as a function of their surface properties.  Our results indicate that the epithelial translocation of DNCs and their uptake into the cell cytosol can be efficiently modulated by varying their surface properties.  These results suggest that incorporating DNCs as drug delivery vehicles in OI strategies can potentially enhance the applicability of OI therapy not only as an effective route for targeting regional ailments but also as an approach to access the systemic portal.