title: Development of fluorous lipid-based nanobubbles for efficiently containing perfluoropropane.
abstract: Nano-/microbubbles are expected not only to function as ultrasound contrast agents but also as ultrasound-triggered enhancers in gene and drug delivery. Notably, nanobubbles have the ability to pass through tumor vasculature and achieve passive tumor targeting. Thus, nanobubbles would be an attractive tool for use as ultrasound-mediated cancer theranostics. However, the amounts of gas carried by nanobubbles are generally lower than those carried by microbubbles because nanobubbles have inherently smaller volumes. In order to reduce the injection volume and to increase echogenicity, it is important to develop nanobubbles with higher gas content. In this study, we prepared 5 kinds of fluoro-lipids and used these reagents as surfactants to generate "Bubble liposomes", that is, liposomes that encapsulate nanobubbles such that the lipids serve as stabilizers between the fluorous gas and water phases. Bubble liposome containing 1-stearoyl-2-(18,18-difluoro)stearoyl-sn-glycero-3-phosphocholine carried 2-fold higher amounts of C3F8 compared to unmodified Bubble liposome. The modified Bubble liposome also exhibited increased echogenicity by ultrasonography. These results demonstrated that the inclusion of fluoro-lipid is a promising tool for generating nanobubbles with increased efficiency of fluorous gas carrier.
authors.affiliation: Laboratory of Drug and Gene Delivery System, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Laboratory of Drug and Gene Delivery System, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Laboratory of Organic Chemistry, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Mori
authors.affiliation: Laboratory of Organic Chemistry, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Laboratory of Organic Chemistry, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Natsugari
authors.affiliation: Laboratory of Drug and Gene Delivery System, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Omata
authors.affiliation: Laboratory of Drug and Gene Delivery System, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Johan
authors.initials: J
authors.lastname: Unga
authors.affiliation: Laboratory of Drug and Gene Delivery System, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Uruga
authors.affiliation: Laboratory of Drug and Gene Delivery System, Faculty of Pharma-Sciences, Teikyo University, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Sugii
authors.affiliation: Analytical Research for Pharmacoinformatics, Graduate School of Biomedical Sciences Medical and Dental Sciences, Nagasaki University, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
authors.affiliation: Laboratory of Drug and Gene Delivery System, Faculty of Pharma-Sciences, Teikyo University, Japan. Electronic address: maruyama@pharm.teikyo-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D003287:Contrast Media; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000737:chemistry; D005740:Gases / Q000008:administration & dosage; D008081:Liposomes / Q000737:chemistry*; D045423:Microbubbles; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D004337:Drug Carriers; D005466:Fluorocarbons; D005740:Gases; D008081:Liposomes; D010743:Phospholipids; C042852:perflutren
keywords: Echogenicity; Fluorous chemistry; Nanobubbles; Ultrasound imaging