<p>The current study aimed to improve the ocular delivery of dexamethasone (DEX) for the treatment of Uveitis. The dexamethasone spanlastics (DEX-SP) were prepared by the thin film hydration method and optimized using the Box Behnken Design. The optimized nanoparticles exhibited an optimum particle size (PS) of 171.9 ± 1.17&#xa0;nm, zeta potential (ZP) of -33.40 ± 0.91 mV, and percentage entrapment efficiency (%EE) of 80.23 ± 3.75%. Physicochemical characterizations, including Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction analysis (XRD), and field emission-scanning electron microscopy (FE-SEM), exhibited favourable properties. The in vitro release of DEX-SP unveiled a sustained release profile with approximately 2.3 times slower release rate than marketed dexamethasone (DEX-M), along with a favorable <i>ex vivo</i> permeation of 498.53 ± 32.68&#xa0;µg/cm<sup>2</sup> over 24&#xa0;h. Furthermore, an endotoxin-induced uveitis (EIU) model was used to assess the formulation’s in vivo anti-inflammatory effectiveness, which revealed that DEX-SP significantly ameliorated endotoxin-induced inflammation. These results were supported by Hogan’s score, hematoxylin and eosin (H&amp;E) staining, and enzyme-linked immunosorbent assay (ELISA), which demonstrated that the DEX-SP reduced tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) levels substantially (<i>p</i> &lt; <i>0.001</i> vs. the negative group). The study indicated that adding DEX to spanlastics promises to improve ocular permeability, absorption, and anti-inflammatory effectiveness while providing a potentially safer and more potent substitute for existing treatment alternatives.</p> Graphical Abstract <p></p>

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Development and Characterization of Dexamethasone-loaded Spanlastics for Ocular Delivery in the Treatment of Uveitis

  • Halla Munir Kayani,
  • Sehrish Ali,
  • Aqeedat Javed,
  • Abeer Tariq,
  • Muhammad Usman,
  • Syeda Komal Fatima,
  • Amna Khan Adil,
  • Nida Javaid,
  • Ismail Badshah,
  • Naqeeb Ullah,
  • Ahmad Khan

摘要

The current study aimed to improve the ocular delivery of dexamethasone (DEX) for the treatment of Uveitis. The dexamethasone spanlastics (DEX-SP) were prepared by the thin film hydration method and optimized using the Box Behnken Design. The optimized nanoparticles exhibited an optimum particle size (PS) of 171.9 ± 1.17 nm, zeta potential (ZP) of -33.40 ± 0.91 mV, and percentage entrapment efficiency (%EE) of 80.23 ± 3.75%. Physicochemical characterizations, including Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction analysis (XRD), and field emission-scanning electron microscopy (FE-SEM), exhibited favourable properties. The in vitro release of DEX-SP unveiled a sustained release profile with approximately 2.3 times slower release rate than marketed dexamethasone (DEX-M), along with a favorable ex vivo permeation of 498.53 ± 32.68 µg/cm2 over 24 h. Furthermore, an endotoxin-induced uveitis (EIU) model was used to assess the formulation’s in vivo anti-inflammatory effectiveness, which revealed that DEX-SP significantly ameliorated endotoxin-induced inflammation. These results were supported by Hogan’s score, hematoxylin and eosin (H&E) staining, and enzyme-linked immunosorbent assay (ELISA), which demonstrated that the DEX-SP reduced tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) levels substantially (p < 0.001 vs. the negative group). The study indicated that adding DEX to spanlastics promises to improve ocular permeability, absorption, and anti-inflammatory effectiveness while providing a potentially safer and more potent substitute for existing treatment alternatives.

Graphical Abstract