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Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

Authors Zhang X, Chen G, Zhang T, Ma Z, Wu B, Wang H

Received 27 August 2014

Accepted for publication 11 October 2014

Published 26 November 2014 Volume 2014:9(1) Pages 5503—5514


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5

Editor who approved publication: Prof. Dr. Thomas J. Webster

Xingwang Zhang,* Guijiang Chen,* Tianpeng Zhang, Zhiguo Ma, Baojian Wu

Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Abstract: Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN), a Biopharmaceutics Classification System (BCS) II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs) were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl®), respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.

Keywords: fenofibrate, lipid nanoparticles, PEGylation, oral bioavailability, absorption mechanism

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