title: Carrier-free nanoassemblies of a novel oxazolidinone compound FYL-67 display antimicrobial activity on methicillin-resistant Staphylococcus aureus.
abstract: In this work, a novel oxazolidinone compound FYL-67 was synthesized, and the obtained FYL-67 could form nanoassemblies in aqueous solution by a self-assembly method without using any carrier, organic solvent, or surfactant. The prepared FYL-67 nanoassemblies had a particle size of 264.6 ± 4.3 nm. The FYL-67 nanoassemblies can be lyophilized into a powder form without any cryoprotector or excipient, and the re-dissolved FYL-67 nanoassemblies are stable and homogeneous. The in vitro release profile showed a significant difference between rapid release of free FYL-67 and much slower and sustained release of FYL-67 nanoassemblies. In vitro susceptibility tests were conducted in three strains of methicillin-susceptible Staphylococcus aureus (MSSA) and three strains of methicillin-resistant Staphylococcus aureus (MRSA), using linezolid as a positive control. FYL-67 nanoassemblies exhibited excellent in vitro activity, with a minimum inhibitory concentration (MIC) value of 0.5 μg mL(-1) against MRSA. In the in vitro post-antibiotic effect (PAE) evaluation, FYL-67 nanoassemblies showed a more powerful effect than linezolid. Besides, in vitro cytotoxicity tests indicated that FYL-67 nanoassemblies had a very low cytotoxicity on HEK293 cells and L02 cells. Furthermore, in both MSSA and MRSA systemic infection mouse models, FYL-67 nanoassemblies showed a lower ED(50) than linezolid. In a murine model of MRSA systemic infection, FYL-67 nanoassemblies displayed an ED(50) of less than 4.0 mg kg(-1), which is 2.3-fold better than that of linezolid. Our findings suggested that the FYL-67 nanoassemblies may be a potential drug candidate in MRSA therapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Ang
authors.forename: Jianying
authors.initials: J
authors.lastname: Tang
authors.forename: Weiyi
authors.initials: W
authors.lastname: Pi
authors.forename: Li
authors.initials: L
authors.lastname: Xiong
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.forename: WeiWei
authors.initials: W
authors.lastname: Ye
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Wang
authors.forename: Youfu
authors.initials: Y
authors.lastname: Luo
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D008422:Materials Testing; D016106:Methicillin Resistance / Q000187:drug effects*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000737:chemistry; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D053769:Nanocapsules; D023303:Oxazolidinones