Nimodipine Nanoparticles: A Promising Approach for Glaucoma Management.

Background/

Objectives

Glaucoma is a multifactorial eye disease that can cause optic nerve damage and irreversible blindness. It is considered a significant public health problem worldwide. Topical intraocular pressure (IOP)-lowering eye preparations are used to prevent or slow further damage. Previously, we demonstrated that nimodipine (NMD), a calcium channel blocker, significantly reduced IOP after a single drop of NMD/HPMC suspension. The current study was designed to develop NMD chitosan nanoparticles (NMD-CS NPs) to improve the NMD IOP-lowering efficacy.

Methods

NMD-CS NPs were prepared using the spontaneous-emulsification solvent diffusion method. Three different types of chitosan, carboxymethyl CS (CMCS), low molecular weight CS (LCS), and medium molecular weight CS (MCS), were used. Different concentrations of polymers, various stabilizers, and two pHs were used for formulation optimization. NMD-CS NPs were characterized regarding their particle size, polydispersity index (PDI), zeta potential, DSC, FTIR, and encapsulation efficiency. NMD-CS NPs were incorporated into eye drops and characterized in terms of their in vitro release, cytotoxicity, transcorneal permeability, and in vivo efficacy.

Results

The optimized NMD-CS NPs demonstrate a small particle size with a narrow size distribution and acceptable zeta potential values. DSC and FTIR results confirmed the complete entrapment of NMD inside the NPs. NMD-CS NP eye drops successfully sustained NMD release without any burst effect. These NPs demonstrated a Higuchi non-Fickian diffusion mechanism and 79.41% improved corneal permeability. Cytotoxicity studies revealed that NMD formulations are nontoxic. After a single topical ocular application, NMD-MCS NP eye drops induced a significantly superior effect to Timolol maleate eye drops with regard to the %IOP reduction and duration of action.

Conclusions

Evaluation results of NMD-CS NP eye drops show their positive effect in a preclinical animal model as a promising glaucoma therapy.