Open Access Dissertation
Date of Award
JOSHUA J. REINEKE
The lungs are an attractive route for drug delivery due to their high epithelial surface area available for absorption, a thin epithelium and extensive vasculature to name a few. Accordingly, a vast number of small molecule drugs, peptides, and proteins have been used to investigate their translocation across the lungs with many of the tested candidates showing excellent pharmacokinetics following pulmonary administration. Findings from all these studies over the years have strongly established the lungs as a route for drug delivery of small molecules and proteins. Nanoparticles on the other hand have gained increasing interest in drug delivery due to the wide variety of advantages they possess that allow for temporal, spatial and targeted delivery of therapeutics that can be fine tuned for various applications. Further, the pulmonary administration of polymeric nanoparticle based drug delivery systems is of great interest for both systemic and localized therapies. However, little is understood about the relationship between nanoparticle size and its effect on pulmonary absorption from a drug delivery perspective. Therefore the aim of this study was to investigate the effect of nanoparticle size on their biodistribution from lungs after pulmonary administration with a special emphasis on their lymph node distribution. Interesting observations were made wherein polystyrene nanoparticles demonstrated significant translocation out of the lungs into extrapulmonary organs. Nanoparticles predominantly deposited in the regional lymph nodes surrounding the lungs as compared to that in other tissues. Furthermore, lymph node deposition of nanoparticles occurred in a time dependent and size dependent manner. The smallest size nanoparticles (50 nm) demonstrated the highest lymph node deposition among all sizes tested and increased with time. Results from this study suggest that nanoparticles may potentially be employed in the treatment of lymph related diseases following pulmonary administration.
Mohammad, Abdul khader, "Investigation of the absorptive potential of polymeric nanoparticles across the lungs and their development for efficient systemic delivery following pulmonary administration" (2012). Wayne State University Dissertations. Paper 552.