Enhanced passive pulmonary targeting and retention of PEGylated rigid microparticles in rats.
The current study examines the passive pulmonary targeting efficacy and retention of 6μm 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 α,ω-diamino poly(ethylene glycol) attached to C-MPs. The ζ-potential of A-MPs (-44.0mV), C-MPs (-54.3mV) and S-MPs (-49.6mV) in deionized water were similar; however PEGylation increased the ζ-potential for both PEG(1)-MPs (-18.3mV) and PEG(2)-MPs (11.5mV). 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 48h 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.
Kutscher
Hilliard L
HL
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Chao
Piyun
P
Deshmukh
Manjeet
M
Sundara Rajan
Sujata
S
Singh
Yashveer
Y
Hu
Peidi
P
Joseph
Laurie B
LB
Stein
Stanley
S
Laskin
Debra L
DL
Sinko
Patrick J
PJ
D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D008168:Lung / Q000378:metabolism; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011137:Polystyrenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D013499:Surface Properties; D014018:Tissue Distribution
D004337:Drug Carriers; D011137:Polystyrenes; D011092:Polyethylene Glycols