Decrease in Corneal Damage due to Benzalkonium Chloride by the Addition of Mannitol into Timolol Maleate Eye Drops

Nagai, Noriaki; Yoshioka, Chiaki; Tanino, Tadatoshi; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

doi:10.5650/jos.ess14275

Cited by 14 publications

(16 citation statements)

References 17 publications

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“…Although it is known that corneal stimulation is a side effect of BAC, the cell viability in treatment with the vehicle was lower than that in cells treated with 0.005% BAC only (61.1 ± 4.9%, n = 7). These low stimulations in the vehicle containing 0.005% BAC were due to the presence of mannitol, since we previously found that mannitol prevents corneal stimulation by BAC [ 38 ]. The viability in HCE-T cells treated with LA-NPs/ISG was similar to those treated by the vehicle.…”

Section: Discussionmentioning

confidence: 99%

“…BAC (0.005%) is a quaternary ammonium compound, and it is used as a preservative in eye drops. It is known that BAC significantly alters precorneal mucins [ 35 ] or induces oxidative stress [ 36 , 37 ], and causes corneal toxicity, and that 0.5% mannitol prevents this BAC toxicity [ 38 ]. Therefore, mannitol can be added to attenuate the corneal toxicity caused by BAC.…”

Section: Discussionmentioning

confidence: 99%

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Ophthalmic In Situ Gelling System Containing Lanosterol Nanoparticles Delays Collapse of Lens Structure in Shumiya Cataract Rats

et al. 2020

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We attempted to prepare ophthalmic in situ gel formulations containing lanosterol (Lan) nanoparticles (LA-NPs/ISG) and investigated the characteristics, delivery pathway into the lens, and anti-cataract effects of LA-NPs/ISG using SCR-N (rats with slight lens structure collapse) and SCR-C (rats with a combination of remarkable lens structure collapse and opacification). LA-NPs/ISG was prepared by bead milling of the dispersions containing 0.5% Lan powder, 5% 2-hydroxypropyl-β-cyclodextrin, 0.5% methylcellulose, 0.005% benzalkonium chloride, and 0.5% mannitol. The particle size distribution of Lan was 60–250 nm. The LA-NPs/ISG was gelled at 37 °C, and the LA-NPs/ISG was taken into the cornea by energy-dependent endocytosis and then released to the intraocular side. In addition, the Lan contents in the lenses of both SCR-N and SCR-C were increased by the repetitive instillation of LA-NPs/ISG (twice per day). The space and structure collapse in the lens of SCR-N with aging was attenuated by the instillation of LA-NPs/ISG. Moreover, the repetitive instillation of LA-NPs/ISG attenuated the changes in cataract-related factors (the enhancement of nitric oxide levels, calpain activity, lipid peroxidation levels, Ca2+ contents, and the decrease of Ca2+-ATPase activity) in the lenses of SCR-C, and the repetitive instillation of LA-NPs/ISG delayed the onset of opacification in the SCR-C. It is possible that the LA-NPs/ISG is useful in maintaining lens homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ophthalmic In Situ Gelling System Containing Lanosterol Nanoparticles Delays Collapse of Lens Structure in Shumiya Cataract Rats

et al. 2020

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“…The abrasion of the corneal epithelium in the normal and STZ rats was performed as described previously [ 41 , 55 , 70 , 71 , 72 , 73 ]. The rats were anesthetized with sodium pentobarbital (30 mg/kg, i.p.…”

Section: Methodsmentioning

confidence: 99%

A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat

Yamamoto

Otake

Hiramatsu

et al. 2018

IJMS

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Diabetes mellitus is a widespread metabolic disorder, and long-term hyperglycemia in diabetics leads to diabetic keratopathy. In the present study, we used a shotgun liquid chromatography/mass spectrometry-based global proteomic approach using the cornea of streptozotocin-induced diabetic (STZ) rats to examine the mechanisms of delayed corneal wound healing in diabetic keratopathy. Applying a label-free quantitation method based on spectral counting, we identified 188 proteins that showed expression changes of >2.0-fold in the cornea of STZ rats. In particular, the level of lumican expression in the cornea of STZ rats was higher than that of the normal rats. In the cornea of the normal rat, the expression level of lumican was elevated during the wound healing process, and it returned to the same expression level as before cornea injury after the wound was healed completely. On the other hand, a high expression level of lumican in the cornea of STZ rats was still maintained even after the wound was healed completely. In addition, adhesion deficiency in corneal basal cells and Bowman’s membrane was observed in the STZ rat. Thus, abnormally overexpressed lumican may lead to adhesion deficiency in the cornea of STZ rats.

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“…First, we prepared nCMFC by the use of additives (methylcellulose (MC), benzalkonium chloride (BAC), and d -mannitol (mannitol)) and the bead mill method. BAC was selected as a preservative, and mannitol was added to prevent the corneal toxicity of BAC [ 26 ]. MC was used to enhance the efficiency of the bead mill [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles

Nagai

Yamaoka

Fukuoka

et al. 2018

IJMS

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We prepared magnesium hydroxide (MH) nanoparticles, and investigated their effect when combined with dissolved carteolol on the bioavailability and intraocular pressure (IOP)-reducing effect of carteolol. The carteolol was solved in saline containing additives (0.5% methylcellulose, 0.001% benzalkonium chloride, 0.5% mannitol; CRT-solution). MH nanoparticles were prepared by a bead mill method with additives. Then carteolol/MH microparticle and carteolol/MH nanoparticle fixed combinations (mCMFC and nCMFC) were prepared by mixing the CRT-solution and MH particles. The transcorneal penetration and IOP-reducing effect of carteolol was evaluated in rabbits. The mean particle size of mCMFC was 7.2 μm, and the particle size was reduced to 73.5–113.5 nm by the bead mill treatment. The MH particles in nCMFC remained in the nano size range for 8 days after preparation, and the amounts of lacrimal fluid and corneal damage were unchanged by repetitive instillation of nCMFC (twice a day for 4 weeks). The transcorneal penetration of carteolol was enhanced by the combination with MH nanoparticles, and the IOP-reducing effect of nCMFC was significantly higher than that of CRT-solution or mCMFC. In conclusion, we designed nCMFC, and showed that the high levels of dissolved carteolol can be delivered into the aqueous humor by the instillation of nCMFC. Combination with MH nanoparticles may achieve an enhancement of corneal penetration for water-soluble drugs. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs.

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Decrease in Corneal Damage due to Benzalkonium Chloride by the Addition of Mannitol into Timolol Maleate Eye Drops

Cited by 14 publications

References 17 publications

Ophthalmic In Situ Gelling System Containing Lanosterol Nanoparticles Delays Collapse of Lens Structure in Shumiya Cataract Rats

Ophthalmic In Situ Gelling System Containing Lanosterol Nanoparticles Delays Collapse of Lens Structure in Shumiya Cataract Rats

A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat

Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles

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