Magnesium Hydroxide Nanoparticles Improve the Ocular Hypotensive Effect of Twice Daily Topical Timolol Maleate in Healthy Dogs.

Mizuki Kita,Kazutaka Kanai,Kazuki Tajima,Hiroki Mitsuhashi,Yuya Otaka,Noriaki Nagai,Yohei Yamashita,Rina Kudo,Mizuki Yamaguchi,Tomoki Noguchi

doi:10.3390/vetsci8080168

Mizuki Kita, Kazutaka Kanai + Show 8 more

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https://doi.org/10.3390/vetsci8080168

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Abstract

Timolol maleate (TM), a beta-adrenergic receptor antagonist, is widely used for canine antiglaucoma eye drops; however, its bioavailability is <5%. Our previous study revealed that magnesium hydroxide nanoparticles (nMH) have potency in improving the bioavailability of fixed-combined TM in rodent models. This study aimed to investigate whether the fixed combination with nMH improves the ocular hypotensive effect of TM and affects pupil size (PS), heart rate (HR), and mean arterial pressure (MAP) in clinically healthy dogs. Five clinically healthy dogs were administered topical saline, commercial 0.5% TM, and a 0.01% or 0.1% nMH–0.5% TM fixed combination (0.01% or 0.1% nMH–TM) twice daily in one eye for 7 days with at least a 28-day interval. The changes from baseline were calculated and were statistically analyzed for each drug. IOP was significantly reduced in both 0.01% and 0.1% nMH–TM-treated-dogs compared with saline- and TM-treated dogs. Meanwhile, 0.01% and 0.1% nMH did not exacerbate the side effects of TM. From these results, nMH improved the ocular hypotensive effect of TM without enhancing side effects. Topical nMH–TM is potentially more effective for canine ocular hypotensive eye drops than TM.

Highlights

Glaucoma is an ocular disease characterized by the progressive death of retinal ganglion cells and their axons [1,2,3,4]
The mainstay of medical glaucoma therapy is aimed at reducing intraocular pressure (IOP), and it is the only evidence-based treatment approved for use in both dogs and humans [1,2,3,4,5,6]
This study aimed to investigate whether the fixed combination with nMH improves the ocular hypotensive effect of timolol maleate (TM) and affects pupil size (PS), heart rate (HR), and mean arterial pressure (MAP) in clinically healthy dogs

Summary

Introduction

Glaucoma is an ocular disease characterized by the progressive death of retinal ganglion cells and their axons [1,2,3,4]. The mainstay of medical glaucoma therapy is aimed at reducing IOP, and it is the only evidence-based treatment approved for use in both dogs and humans [1,2,3,4,5,6]. There are a numerous commercially available antiglaucoma eye drops, including beta-adrenergic receptor antagonists, miotics, carbonic anhydrase inhibitors, and prostaglandin analogs. TM is one of the most widely used antiglaucoma eye drops in combination with other drugs to treat both canine and human patients. TM reduces IOP by decreasing the production of the aqueous humor and blocking the beta-adrenergic receptor in ciliary body nonpigmented epithelial cells [10,11]. As for other local effects, TM affects contralateral IOP and pupil size (PS)

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