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 μm polystyrene (PS) microparticles (MPs) covalently modified with different surface groups [amine (A-), carboxyl (C-) and sulfate (S-)] or single (PEG1-) and double (PEG2-) layers of α,ω-diamino poly(ethylene glycol) attached to C-MPs. The ζ-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 ζ-potential for both PEG1-MPs (−18.3 mV) and PEG2-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. PEG1-MPs and PEG2-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.

Graphical abstractThe lung retention of rigid 6 μm polystyrene microparticles (MPs) intravenously administered to rats was investigated. MPs with different surface groups [amine (A-), carboxylate (C-) or sulfate (S-)] or poly(ethylene glycol) (PEG) layers [single (PEG1-) or double (PEG2-)] were used. The lung retention of the unmodified MPs (A-, C- and S-MPs) is similar and their resulting AUCs are statistically different than the AUCs of the PEGylated MPs by one-way ANOVA.Figure optionsDownload full-size imageDownload as PowerPoint slide