PEGylated inulin as long-circulating pharmaceutical carrier.
Although poly(ethylene glycol) and polysaccharide have been widely used as pharmaceutical carriers for decades, they both have some disadvantages. In order to overcome these shortcomings, this study was conducted to prepare and assess a novel polymeric carrier, PEGylated inulin. Three conjugates, with an average of 1.4 PEG (20 kDa), 3.1 PEG (20 kDa) and 5.5 PEG (5 kDa) residues per single inulin (5 kDa) molecule, respectively, were prepared through the reaction of hydroxyl-activated inulin with amino-terminated methoxy-PEGs. Their pharmacokinetic properties were evaluated in rats following i.v. and s.c. administration. These conjugates, following i.v. administration, displayed multi-compartmental pharmacokinetics with the mean retention times being 9.8, 80 and 90 h, respectively. When given subcutaneously, they were well absorbed with the absolute bioavailability ranging from 66% to 79% and the mean retention times being 35, 155 and 179 h, respectively. Both the small size and the long circulation lifetime suggest their potential application as a pharmaceutical carrier to enhance the delivery of various agents to their targets by the enhanced permeability and retention (EPR) effect.
Sun
Guilan
G
College of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Lin
Xiao
X
Wang
Zhuojun
Z
Feng
Yi
Y
Xu
Desheng
D
Shen
Lan
L
D000818:Animals; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D007444:Inulin / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
D004337:Drug Carriers; D011092:Polyethylene Glycols; D007444:Inulin