Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design

Area of Science:

• Ophthalmology
• Nanotechnology
• Pharmaceutics

Background:

• Glaucoma treatment often involves topical medications to reduce intraocular pressure.
• Developing effective drug delivery systems for ophthalmic drugs is crucial for improving therapeutic outcomes.
• Methazolamide (MTZ) is a carbonic anhydrase inhibitor used to treat glaucoma, but its topical delivery presents challenges.

Purpose of the Study:

• To optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) for topical ophthalmic delivery.
• To evaluate the relationship between formulation design factors and experimental data for MTZ-SLNs.
• To assess the in vivo efficacy, safety, and stability of the optimized MTZ-SLNs.

Main Methods:

• A Box-Behnken design (BBD) was employed to optimize SLN formulation variables (GMS, phospholipid, surfactant concentration).
• Dependent variables included entrapment efficiency, dosage loading, and particle size.
• Characterization involved particle size analysis, polydispersity index, zeta potential, FT-IR, in vivo pharmacodynamics, and eye irritation studies.

Main Results:

• Optimized MTZ-SLNs (100 mg GMS, 150 mg phospholipid, 1% surfactant) achieved 197.8 nm particle size, 68.39% entrapment efficiency, and 2.49% dosage loading.
• The formulation exhibited sustained drug release following the Peppas model.
• In vivo studies showed a prolonged intraocular pressure-lowering effect compared to MTZ solution, with no observed eye irritation and good storage stability at 4°C.

Conclusions:

• The optimized MTZ-SLNs provide an effective and safe topical drug delivery system for glaucoma management.
• The BBD approach successfully optimized the SLN formulation for enhanced ophthalmic drug delivery.
• MTZ-SLNs offer a promising alternative to conventional MTZ solutions, improving therapeutic efficacy and patient compliance.