Nanostructured Lipid Carriers for Enhanced Transscleral Delivery of Dexamethasone Acetate: Development, Ex Vivo Characterization and Multiphoton Microscopy Studies

Corticosteroids, although highly effective for the treatment of both anterior and posterior ocular segment inflammation, still nowadays struggle for effective drug delivery due to their poor solubilization capabilities in water. This research work aims to develop nanostructured lipid carriers (NLC) intended for periocular administration of dexamethasone acetate to the posterior segment of the eye. Pre-formulation studies were initially performed to find solid and liquid lipid mixtures for dexamethasone acetate solubilization. Pseudoternary diagrams at 65 degrees C were constructed to select the best surfactant based on the macroscopic transparency and microscopic isotropy of the systems. The resulting NLC, obtained following an organic solvent-free methodology, was composed of triacetin, Imwitor (R) 491 (glycerol monostearate >90%) and tyloxapol with Z-average = 106.9 +/- 1.2 nm, PDI = 0.104 +/- 0.019 and zeta potential = -6.51 +/- 0.575 mV. Ex vivo porcine sclera and choroid permeation studies revealed a considerable metabolism in the sclera of dexamethasone acetate into free dexamethasone, which demonstrated higher permeation capabilities across both tissues. In addition, the NLC behavior once applied onto the sclera was further studied by means of multiphoton microscopy by loading the NLC with the fluorescent probe Nile red.

Automated summary

This research aims to develop nanostructured lipid carriers (NLC) for periocular administration of dexamethasone acetate for the treatment of ocular inflammation. The NLC was formulated using solid and liquid lipid mixtures, resulting in a particle size of 106.9 +/- 1.2 nm, PDI = 0.104 +/- 0.019, and zeta potential = -6.51 +/- 0.575 mV. Ex vivo permeation studies showed that dexamethasone acetate was metabolized into free dexamethasone and exhibited higher permeation capabilities across both sclera and choroid tissues.