title: Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation.
abstract: Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also discounted. The aim of this study is to develop a long-circulating prostaglandin E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1 nanoemulsion was prepared using a dispersing-homogenized method. The stability of nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed to evaluate the in vivo profile of the optimized nanoemulsion. The optimized nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size <100 nm with a surface charge of -14 mV. Approximately, 97% of the PGE1 was encapsulated in the nanoemulsion. The particle size, zeta potential, and drug loading of PGE1-PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was intravenously administered to rats, the area under curve (AUC) and half-life of PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1 (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for prolonging the elimination time of PGE1. This novel parenteral colloidal delivery system of PGE1 has a promising potential in clinic use.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Xi'an Libang Zhaoxin Biological Technology Co., Ltd., Xi'an, 710061, China.
authors.forename: Huijing
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Daozhou
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China. zhousy@fmmu.edu.cn.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000527:Alprostadil / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004655:Emulsions / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D006207:Half-Life; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004655:Emulsions; D005079:Excipients; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D000527:Alprostadil
keywords: LC-MS/MS; nanoemulsion; pharmacokinetic; polyethylene glycol; prostaglandin E1