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Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats.

Li Z, Yao L, Li J, Zhang W, Wu X, Liu Y, Lin M, Su W, Li Y, Liang D - Int J Nanomedicine (2012)

Bottom Line: In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.

ABSTRACT

Purpose: 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.

Conclusion: 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.

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The structure of (A) celastrol and (B) poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles and (C) schematic illustration of celastrol-loaded micelle formation.Abbreviation: PEG-b-PCL, poly(ethylene glycol)-block-poly(ɛ-caprolactone).
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f1-ijn-7-1163: The structure of (A) celastrol and (B) poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles and (C) schematic illustration of celastrol-loaded micelle formation.Abbreviation: PEG-b-PCL, poly(ethylene glycol)-block-poly(ɛ-caprolactone).

Mentions: Chinese herbal celastrol (Figure 1A) was purchased from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences (Shanghai, China). Celastrol-loaded PEG-b-PCL micelles were prepared by dissolving PEG-b-PCL (2000:1000, weight-average molecular weight/number average molecular weight: 1.18; JCS Biopolytech Inc, Toronto, ON, Canada; Figure 1B) (10 mg) and celastrol (2 mg) in chloroform (2 mL) and adding this solution dropwise to double-distilled water (20 mL) under ultrasonic agitation using a sonic dismembrator (model 60; Thermo Fisher Scientific, Pittsburgh, PA) at a power level of 30. The organic solvent was then removed by vacuum distillation using a rotary evaporator to allow micelle formation. The samples were further concentrated and washed three times to remove insoluble material and unincorporated drug through a 0.22 μm polyethersulfone filter. A schematic illustration of celastrol-loaded micelle formation is shown in Figure 1C.


Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats.

Li Z, Yao L, Li J, Zhang W, Wu X, Liu Y, Lin M, Su W, Li Y, Liang D - Int J Nanomedicine (2012)

The structure of (A) celastrol and (B) poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles and (C) schematic illustration of celastrol-loaded micelle formation.Abbreviation: PEG-b-PCL, poly(ethylene glycol)-block-poly(ɛ-caprolactone).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3298384&req=5

f1-ijn-7-1163: The structure of (A) celastrol and (B) poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles and (C) schematic illustration of celastrol-loaded micelle formation.Abbreviation: PEG-b-PCL, poly(ethylene glycol)-block-poly(ɛ-caprolactone).
Mentions: Chinese herbal celastrol (Figure 1A) was purchased from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences (Shanghai, China). Celastrol-loaded PEG-b-PCL micelles were prepared by dissolving PEG-b-PCL (2000:1000, weight-average molecular weight/number average molecular weight: 1.18; JCS Biopolytech Inc, Toronto, ON, Canada; Figure 1B) (10 mg) and celastrol (2 mg) in chloroform (2 mL) and adding this solution dropwise to double-distilled water (20 mL) under ultrasonic agitation using a sonic dismembrator (model 60; Thermo Fisher Scientific, Pittsburgh, PA) at a power level of 30. The organic solvent was then removed by vacuum distillation using a rotary evaporator to allow micelle formation. The samples were further concentrated and washed three times to remove insoluble material and unincorporated drug through a 0.22 μm polyethersulfone filter. A schematic illustration of celastrol-loaded micelle formation is shown in Figure 1C.

Bottom Line: In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.

ABSTRACT

Purpose: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus