title: Lipid transfer protein transports compounds from lipid nanoparticles to plasma lipoproteins.
abstract: Nanometer-sized lipid emulsion particles with a diameter of 25-50 nm, called Lipid Nano-Sphere (LNS), are expected as a promising drug carrier to show prolonged plasma half-life of an incorporating drug. In terms of successful drug delivery using LNS, a drug should be incorporated into the lipid particles and remain within the particle, not only in the formulation in vitro but also after administration into the systemic blood circulation. In this study, we showed that phospholipids and some water-insoluble molecules also moved from lipid particles to plasma lipoproteins or albumin in serum and plasma half-lives of these compounds did not reflect that of the drug carriers. It was suggested that phospholipid or its derivative were transferred from LNS particles to plasma lipoproteins by lipid transfer proteins (LTP) in the circulation. These phenomena leaded to unsuccessful delivery of the drug with lipid-particulate drug carriers. On the other hand, lipophilic derivatives with cholesterol pro-moiety tested in this study were not released from LNS particles and showed prolonged plasma half-lives. Lipophilicity is known to be an important parameter for incorporating drugs into lipid particles but substrate specificity for LTP seems to be another key to success promising drug design using lipid emulsion particulate delivery system.
authors.affiliation: Pharmacy Laboratories, Nippon Shinyaku Co. Ltd., 14, Nishinosho-Monguchicho, Kissyoin, Minami-Ku, Kyoto 601-8550, Japan. j.seki@po.nippon-shinyaku.co.jp
authors.forename: Junzo
authors.initials: J
authors.lastname: Seki
authors.forename: Satoru
authors.initials: S
authors.lastname: Sonoke
authors.forename: Akira
authors.initials: A
authors.lastname: Saheki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Koike
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
authors.forename: Masaharu
authors.initials: M
authors.lastname: Doi
authors.forename: Tadanori
authors.initials: T
authors.lastname: Mayumi
mesh_terms: D000818:Animals; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004337:Drug Carriers; D004655:Emulsions; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D036103:Nanotechnology; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001798:Blood Proteins; D002352:Carrier Proteins; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D008074:Lipoproteins; D008081:Liposomes; C030363:lipid transfer protein; D016685:Mitomycin