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Journal of Nanoparticle Research

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01-10-2013 | Research Paper

Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG–PLA micelle

Authors: Yanan Shi, Fengying Sun, Dan Wang, Renyu Zhang, Changlin Dou, Wanhui Liu, Kaoxiang Sun, Youxin Li

Published in: Journal of Nanoparticle Research | Issue 10/2013

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Abstract

A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG–PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from −0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG–PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.

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Title: Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG–PLA micelle
Authors: Yanan Shi
Fengying Sun
Dan Wang
Renyu Zhang
Changlin Dou
Wanhui Liu
Kaoxiang Sun
Youxin Li
Publication date: 01-10-2013
Publisher: Springer Netherlands
Published in: Journal of Nanoparticle Research / Issue 10/2013
Print ISSN: 1388-0764
Electronic ISSN: 1572-896X
DOI: https://doi.org/10.1007/s11051-013-2002-x

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