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