Open Access Dissertation
Date of Award
Chemical Engineering and Materials Science
Sandro R. da Rocha
The lungs are considered as one of the fastest portals of entry to the bloodstream and oral inhalation (OI) has long been accepted as the preferred mode of administration of therapeutics to the respiratory tract. However, despite its advantages, the lungs have been largely underutilized to target ailments not only of systemic relevance but also several other grave conditions including lung cancer and tuberculosis. Polymeric nanocarriers (PNCs) have several advantages over other drug delivery vehicles including sustained release of moieties, ease of cellular internalization and improved targeting, and hence hold the promise to greatly augment the potential of OI therapies. The surface chemistry, architecture, and size of PNCs may be potentially altered in order to modulate their interaction with the extra and intracellular barriers present in the lung epithelia, and thus their transport, overcoming challenges observed when delivering free drug molecules. They can be utilized to enhance the residence time of drugs required to exert prolonged therapeutic effect in the airspace (regional therapy), and conversely speed up the transport of drug molecules that would traverse sluggishly to the bloodstream (systemic therapy). In this work, we report the preparation, characterization of a series of PNCs ranging from polymeric nanoparticles (PNPs) to surface modified dendrimer nanocarriers (DNCs) and we studied their interaction with in vitro and in vivo models of the lung epithelium. We observed that transport and cellular uptake can be efficiently modulated as the surface characteristics of the PNCs is varied, suggesting that OI strategies incorporating such nanoscopic entities may potentially be employed for targeting regional diseases and also the systemic circulation. Finally, we also discuss the formulation, dispersion stability and aerosol characteristics of the aforementioned PNCs in portable, inexpensive pressurized metered dose inhalers (pMDIs).
Bharatwaj, Balaji, "Polymeric nanocarriers for the regional and systemic delivery of therapeutics to and through the lungs" (2012). Wayne State University Dissertations. 426.