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Original Research

High drug payload nanoparticles formed from dexamethasone-peptide conjugates for the treatment of endotoxin-induced uveitis in rabbit

, , , &
Pages 591-603 | Published online: 14 Jan 2019

Figures & data

Figure 1 Chemical structure of the Dex-SA-FFFE conjugate.

Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure 1 Chemical structure of the Dex-SA-FFFE conjugate.Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure 2 (A) TEM image of Dex-SA-FFFE nanoparticles and (B) size distribution of Dex-SA-FFFE nanoparticles.

Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure 2 (A) TEM image of Dex-SA-FFFE nanoparticles and (B) size distribution of Dex-SA-FFFE nanoparticles.Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure 3 In vitro release profiles of Dex and Dex-SA-FFFE from Dex-SA-FFFE nanoparticles in (A) PBS (pH =7.4) and (B) PBS (pH =7.4) containing 20 U/mL esterase.

Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure 3 In vitro release profiles of Dex and Dex-SA-FFFE from Dex-SA-FFFE nanoparticles in (A) PBS (pH =7.4) and (B) PBS (pH =7.4) containing 20 U/mL esterase.Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure 4 In vitro cytotoxicity of Dex-SA-FFFE nanoparticles against HCEC after 24, 48, and 72 hours of incubation.

Abbreviations: Dex-SA-FFFE, dexamethasone-peptide conjugate; HCEC, human corneal epithelial cell.

Figure 4 In vitro cytotoxicity of Dex-SA-FFFE nanoparticles against HCEC after 24, 48, and 72 hours of incubation.Abbreviations: Dex-SA-FFFE, dexamethasone-peptide conjugate; HCEC, human corneal epithelial cell.

Figure 5 Inhibition of (A) NO, (B) TNF-α, and (C) IL-6 production by Dex-SA-FFFE nanoparticles and Dex in LPS-stimulated RAW264.7 macrophages. *P<0.05, when compared to LPS group.

Abbreviations: Dex-SA-FFFE, dexamethasone-peptide conjugate; IL-6, interleukin-6; LPS, lipopolysaccharide; NO, nitric oxide; TNF-α, tumor necrosis factor-α.

Figure 5 Inhibition of (A) NO, (B) TNF-α, and (C) IL-6 production by Dex-SA-FFFE nanoparticles and Dex in LPS-stimulated RAW264.7 macrophages. *P<0.05, when compared to LPS group.Abbreviations: Dex-SA-FFFE, dexamethasone-peptide conjugate; IL-6, interleukin-6; LPS, lipopolysaccharide; NO, nitric oxide; TNF-α, tumor necrosis factor-α.

Figure 6 (A) Clinical signs of anterior uveitis in rabbits treated with PBS, Dexp, and Dex-SA-FFFE nanoparticles. White arrowheads indicate inflammatory exudates in the anterior chamber. (B) H&E sections of rabbit eyes treated with PBS, Dexp, and Dex-SA-FFFE nanoparticles at 24 hours after challenge with LPS. White arrowheads indicate inflammatory cells infiltration in the anterior chamber.

Abbreviations: Dex-SA-FFFE, dexamethasone-peptide conjugate; Dexp, Dex sodium phosphate; H&E, hematoxylin and eosin; LPS, lipopolysaccharide.

Figure 6 (A) Clinical signs of anterior uveitis in rabbits treated with PBS, Dexp, and Dex-SA-FFFE nanoparticles. White arrowheads indicate inflammatory exudates in the anterior chamber. (B) H&E sections of rabbit eyes treated with PBS, Dexp, and Dex-SA-FFFE nanoparticles at 24 hours after challenge with LPS. White arrowheads indicate inflammatory cells infiltration in the anterior chamber.Abbreviations: Dex-SA-FFFE, dexamethasone-peptide conjugate; Dexp, Dex sodium phosphate; H&E, hematoxylin and eosin; LPS, lipopolysaccharide.

Figure 7 (A) Leucocytes counts, (B) TNF-α, and (C) IL-6 levels in the aqueous humor of EIU rabbits after topical treatment by PBS, Dexp, and Dex-SA-FFFE nanoparticles. **P<0.05, when compared to PBS group.

Abbreviations: Dex-SA-FFFE, dexamethasone-peptide conjugate; Dexp, Dex sodium phosphate; EIU, endotoxin-induced uveitis; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α.

Figure 7 (A) Leucocytes counts, (B) TNF-α, and (C) IL-6 levels in the aqueous humor of EIU rabbits after topical treatment by PBS, Dexp, and Dex-SA-FFFE nanoparticles. **P<0.05, when compared to PBS group.Abbreviations: Dex-SA-FFFE, dexamethasone-peptide conjugate; Dexp, Dex sodium phosphate; EIU, endotoxin-induced uveitis; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α.

Figure S1 LC-MS spectra of Dex-SA-FFFE.

Figure S1 LC-MS spectra of Dex-SA-FFFE.

Figure S2 Appearance of Dex-SA-FFFE suspension before (left) and after (right) heating-cooling circle.

Figure S2 Appearance of Dex-SA-FFFE suspension before (left) and after (right) heating-cooling circle.

Figure S3 LC-MS spectra of Dex-SA-FFFE nanoparticles formed after heating-cooling circle.

Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure S3 LC-MS spectra of Dex-SA-FFFE nanoparticles formed after heating-cooling circle.Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.
Figure S3 LC-MS spectra of Dex-SA-FFFE nanoparticles formed after heating-cooling circle.Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure S4 Slit-lamp image and fluorescein staining of cornea at 3days post topical instillation of phosphate buffered saline (PBS) and Dex-SA-FFFE nanoparticles.

Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure S4 Slit-lamp image and fluorescein staining of cornea at 3days post topical instillation of phosphate buffered saline (PBS) and Dex-SA-FFFE nanoparticles.Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure S5 The changes of intraocular pressure after instillation of phosphate buffered saline (PBS, pH=7.4) and Dex-SA-FFFE nanoparticles.

Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure S5 The changes of intraocular pressure after instillation of phosphate buffered saline (PBS, pH=7.4) and Dex-SA-FFFE nanoparticles.Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure S6 The changes of corneal thickness after instillation of phosphate buffered saline (PBS, pH=7.4) and Dex-SA-FFFE nanoparticles.

Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.

Figure S6 The changes of corneal thickness after instillation of phosphate buffered saline (PBS, pH=7.4) and Dex-SA-FFFE nanoparticles.Abbreviation: Dex-SA-FFFE, dexamethasone-peptide conjugate.