title: Preparation and characterization of 5-fluorouracil pH-sensitive niosome and its tumor-targeted evaluation: in vitro and in vivo.
abstract: The purpose of this study was to investigate preparation, characterization and tumor-targeted effect of pH-sensitive niosomes, composed of a nonionic surfactant mixed with cholesteryl hemisuccinate (CHEMS), a derivative of cholesterol (CHOL), as a pH-sensitive molecule. CHEMS was synthesized with CHOL and succinic acid, the structure of which was analyzed by Mass spectrometry (MS) and ¹H Nuclear magnetic resonance (¹H NMR) spectrum. Niosomes were prepared via film hydration-probe ultrasound method. Both normal niosomes and pH-sensitive niosomes showed spherical morphology under transmission electron microscope (TEM) with a average particle sizes of 172 ± 6.2 nm and 153 ± 4.7 nm, respectively. The thermotropic behavior, structure changes and interaction of 5-fluorouracil (5-Fu) with other materials were characterized by differential scanning calorimetry (DSC), and the disappearance of the melting peak of drug revealed the fact that drug was encapsulated in niosomes. Bulk-equilibrium reverse-dialysis method was chosen to investigate the behavior of drug release from normal niosomes and pH-sensitive niosomes in different pH medium, and the results showed that the noisome containing CHEMS had a pH-sensitive property. Tumor-targeted effect was proved by the fact that pH-sensitive niosomes showed a remarkable high concentration in tumor site of the mice transplanted with tumor cell.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. wangmi27@163.com
authors.forename: Mi
authors.initials: M
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Ma
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Zhang
authors.forename: Wei-San
authors.initials: WS
authors.lastname: Pan
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D002788:Cholesterol Esters / Q000737:chemistry; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D051379:Mice; D008815:Mice, Inbred Strains; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010316:Particle Size; D011897:Random Allocation; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D002788:Cholesterol Esters; D005079:Excipients; D008081:Liposomes; D013501:Surface-Active Agents; C013440:cholesteryl succinate; D005472:Fluorouracil