Formulation and Pathohistological Study of Mizolastine–Solid Lipid Nanoparticles–Loaded Ocular Hydrogels

BACKGROUND: Mizolastine (MZL) is a dual-action nonsedating topical antihistamine anti-inflammatory agent that is used to relieve allergic conditions, such as rhinitis and conjunctivitis. Solid lipid nanoparticles (SLNs) are advanced delivery system in ophthalmology, with the merits of increasing the corneal drug absorption and hence improved bioavailability with the objective of ocular drug targeting. METHODS: First, MZL was formulated as MZL-SLNs by hot homogenization/ultrasonication adopting a 3(2) full factorial design. Solid-state characterization, in vitro release, and stability studies have been performed. Then, the optimized MZL-SLNs formula has been incorporated into ocular hydrogels using 1.5% w/v Na alginate and 5% w/v polyvinylpyrrolidone K(90). The gels were evaluated via in vitro release as well as in vivo studies by applying allergic conjunctivitis congestion in a rabbit-eye model. RESULTS: The optimized formula (F4) was characterized by the highest entrapment efficiency (86.5±1.47%), the smallest mean particle size (202.3±13.59 nm), and reasonable zeta potential (−22.03±3.65 mV). Solid-state characterization of the encapsulation of MZL in SLNs was undertaken. In vitro results showed a sustained release profile from MZL-SLNs up to 30 hours with a non-Fickian Higuchi kinetic model. Stability studies confirmed immutability of freeze-dried MZL-SLNs (F4) upon storage for 6 months. Finally, hydrogel formulations containing MZL-SLNs, proved ocular congestion disappearance with completely repaired conjunctiva after 24 hours. Moreover, pretreatment with MZL-SLNs–loaded hydrogel imparted markedly decreased TNF-α and VEGF-expression levels in rabbits conjunctivae compared with post-treatment with the same formula. CONCLUSION: MZL-SLNs could be considered a promising stable sustained-release nanoparticulate system for preparing ocular hydrogel as effective antiallergy ocular delivery systems.