title: Enhanced antifungal effects of amphotericin B-TPGS-b-(PCL-ran-PGA) nanoparticles in vitro and in vivo.
abstract: BACKGROUND
  Amphotericin B (AMB) is a polyene antibiotic with broad spectrum antifungal activity, but its clinical toxicities and poor solubility limit the wide application of AMB in clinical practice. Recently, new drug-loaded nanoparticles (NPs) - diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (PLGA-TPGS) - have received special attention for their reduced toxicity, and increased effectiveness of drug has also been reported. This study aimed to develop AMB-loaded PLGA-TPGS nanoparticles (AMB-NPs) and evaluate their antifungal effects in vitro and in vivo.
  
  
  METHODS
  AMB-NPs were prepared with a modified nanoprecipitation method and then characterized in terms of physical characteristics, in vitro drug release, stability, drug-encapsulation efficiency, and toxicity. Finally, the antifungal activity of AMB-NPs was investigated in vitro and in vivo.
  
  
  RESULTS
  AMB-NPs were stable and spherical, with an average size of around 110 nm; the entrapment efficacy was closed to 85%, and their release exhibited a typically biphasic pattern. The actual minimum inhibitory concentration of AMB-NPs against Candida albicans was significantly lower than that of free AMB, and AMB-NPs were less toxic on blood cells. In vivo experiments indicated that AMB-NPs achieved significantly better and prolonged antifungal effects when compared with free AMB.
  
  
  CONCLUSIONS
  The AMB-PLGA-TPGS NP system significantly improves the AMB bioavailability by improving its antifungal activities and reducing its toxicity, and thus, these NPs may become a good drug carrier for antifungal treatment.
authors.affiliation: Stem Cell Engineering Research Center, School of Medicine, Anhui University of Science and Technology, Huainan, People's Republic of China ; State Key Laboratory of Virology, Life Sciences College, Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Institute of Skin Damage and Repair, General Hospital of Beijing Military Command, Beijing, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ledong
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Virology, Life Sciences College, Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.affiliation: Stem Cell Engineering Research Center, School of Medicine, Anhui University of Science and Technology, Huainan, People's Republic of China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Cai
authors.affiliation: Stem Cell Engineering Research Center, School of Medicine, Anhui University of Science and Technology, Huainan, People's Republic of China.
authors.forename: Rongbo
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Children's Hospital, Chongqing Medical University; Key Laboratory of Child Development and Disorders of the Ministry of Education, Chongqing, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000382:microbiology; D015169:Colony Count, Microbial; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D005026:Ethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D005026:Ethylene Glycols; D011091:Polyesters; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D014810:Vitamin E; D011092:Polyethylene Glycols; D000666:Amphotericin B; C014225:tocophersolan
keywords: C. albicans; amphotericin B; anti-infection; drug delivery; nanocarrier