title: Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats.
abstract: OBJECTIVE
  Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and determine the possible mechanism.
  
  
  METHODS
  To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea.
  
  
  RESULTS
  The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial cells in a dose-independent manner and suppressed the capillary structure formation. After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm(2) to 2.29 ± 0.61 mm(2), respectively. Macrophage infiltration decreased significantly in the CNP-treated corneas. CNPs reduced the expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea on day 6 after suturing.
  
  
  CONCLUSIONS
  CNPs significantly inhibited suture-induced CNV by suppressing macrophage infiltration and the expression of vascular endothelial growth factor and matrix metalloproteinase 9 in the rat cornea.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Zhanrong
authors.initials: Z
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Yao
authors.forename: Jingguo
authors.initials: J
authors.lastname: Li
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zhang
authors.forename: Xianghua
authors.initials: X
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Miaoli
authors.initials: M
authors.lastname: Lin
authors.forename: Wenru
authors.initials: W
authors.lastname: Su
authors.forename: Yongping
authors.initials: Y
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003315:Cornea / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D016510:Corneal Neovascularization / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006651:Histocytochemistry; D061307:Human Umbilical Vein Endothelial Cells; D007150:Immunohistochemistry; D007783:Lactones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D053978:Pentacyclic Triterpenes; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013537:Sutures; D014315:Triterpenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D004337:Drug Carriers; D007783:Lactones; D008823:Micelles; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D042461:Vascular Endothelial Growth Factor A; C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; D020780:Matrix Metalloproteinase 9; C050414:celastrol