Rapid Lymph Accumulation of Polystyrene Nanoparticles Following Pulmonary Administration
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RESEARCH PAPER
Rapid Lymph Accumulation of Polystyrene Nanoparticles Following Pulmonary Administration Abdul Khader Mohammad & Lenah K. Amayreh & John M. Mazzara & Joshua J. Reineke
Received: 4 May 2012 / Accepted: 5 September 2012 / Published online: 20 September 2012 # Springer Science+Business Media, LLC 2012
ABSTRACT Purpose Pulmonary administration of polymeric nanoparticle drug delivery systems is of great interest for both systemic and local therapies. However, little is understood about the relationship of particle size and pulmonary absorption. We investigated uptake and biodistribution of polystyrene nanoparticles (PN) of 50 nm, 100 nm, 250 nm, and 900 nm diameters in mice following administration to lungs via pharyngeal aspiration. Methods The amount of PN in tissues was analyzed by gel permeation chromatography (GPC). Results At 1 h, larger diameter PN (250 nm and 900 nm) had the highest total uptake at around 15% of administered dose, whereas the smaller diameter PN (50 nm and 100 nm) had uptake of only 5–6%. However, at 3 h, the 50 nm PN had the highest total uptake at 24.4%. For each size tested, the highest nanoparticle deposition was observed in the lymph nodes (LN) as compared to other tissues accounting for a total of about 35– 50% of absorbed nanoparticles. Conclusion PN size impacts the rate and extent of uptake from lungs and, further, the extent of LN deposition. The extent of uptake and lymph distribution of the model, non-degradable PN lends potential to pulmonary administered, biodegradable polymeric nanoparticles for delivery of therapeutics to regional lymph nodes. Electronic supplementary material The online version of this article (doi:10.1007/s11095-012-0884-4) contains supplementary material, which is available to authorized users. A. K. Mohammad : L. K. Amayreh : J. M. Mazzara : J. J. Reineke Department of Pharmaceutical Sciences Eugene Applebaum College of Pharmacy & Health Sciences Wayne State University Detroit, Michigan 48201, USA J. J. Reineke (*) Wayne State University Room 3136, Eugene Applebaum Building, 259 Mack Avenue Detroit, Michigan 48201, USA e-mail: [email protected]
KEY WORDS biodistribution . lymph node . pharyngeal aspiration . polystyrene nanoparticle . pulmonary delivery ABBREVIATIONS ALN axillary lymph nodes BAL bronchoalveolar lavage BLN brachial lymph nodes CLN cervical lymph nodes DLS dynamic light scattering GPC gel permeation chromatography H&E hematoxylin and eosin LN lymph node(s) PN polystyrene nanoparticles RES reticuloendothelial system RI refractive index TEM transmission electron microscopy
INTRODUCTION The lungs possess many advantages as an administration pathway including an alveolar surface area of around 100 m2 (1), high solute permeability, limited proteolytic activity (2), a very thin alveolar epithelium of 0.2 μm, and extensive vasculature (3). Considerable research has been carried out in investigating and improving the pharmacokinetics of several drugs, peptides and proteins from the lungs (4–8). In the field of pulmonary drug delivery,
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