Enhanced passive pulmonary targeting and retention of PEGylated rigid microparticles in rats

The current study examines the passive pulmonary targeting efficacy and retention of 6 mu m polystyrene (PS) microparticles (MPs) covalently modified with different surface groups [amine (A-), carboxyl (C-) and sulfate (S-)] or single (PEG(1)-) and double (PEG(2)-) layers of alpha,omega-diamino poly(ethylene glycol) attached to C-MPs. The zeta-potential of A-MPs (-44.0 mV), C-MPs (-54.3 mV) and S-MPs (-49.6 mV) in deionized water were similar; however PEGylation increased the zeta-potential for both PEG(1)-MPs (-18.3 mV) and PEG(2)-MPs (11.5 mV). The biodistribution and retention of intravenously administered MPs to male Sprague-Dawley rats was determined in homogenized tissue by fluorescence spectrophotometry. PEG(1)-MPs and PEG(2)-MPs demonstrated enhanced pulmonary retention in rats at 48 h after injection when compared to unmodified A-MPs (59.6%, 35.9% and 17.0% of the administered dose, respectively). While unmodified MPs did not significantly differ in lung retention. PEGylation of MPs unexpectedly improved passive lung targeting and retention by modifying surface properties including charge and hydrophobicity but not size. (C) 2010 Published by Elsevier B.V.