• Home
  • Search Results
  • A nanoparticle formulation reduces the corneal toxicity of indomethacin eye drops and enhances its corneal permeability.

A nanoparticle formulation reduces the corneal toxicity of indomethacin eye drops and enhances its corneal permeability.

Toxicology (2014-03-07)
Noriaki Nagai, Yoshimasa Ito, Norio Okamoto, Yoshikazu Shimomura
ABSTRACT

Indomethacin (IMC) has been shown to reduce post-operative inflammation and to decrease intraocular irritation after cataract extraction and in cystoid macular edema; however, the clinical use of its most commonly used eye drops is limited due to topical side-effects that include burning sensation, irritation and epithelial keratitis. It is known that decreasing direct cell stimulation and reducing the amount applied via increasing bioavailability are useful for improving these issues. In this study, we designed ophthalmic formulations containing 0.5% IMC nanoparticles using zirconia beads and Bead Smash 12 (IMCnano eye drops; particle size 76 ± 59 nm, mean ± S.D.), and investigated the corneal toxicity of these IMCnano eye drops. IMCnano eye drops are tolerated better by a human cornea epithelial cell line (HCE-T) than commercially available NDSAIDs preparations (IMC, pranoprofen, diclofenac, bromfenac and nepafenac eye drops), and corneal wound healing in rat eyes with debrided corneal epithelium instilled with IMCnano eye drops is significantly better than that of eyes instilled with commercially available IMC eye drops. In addition, the accumulation of IMC in HCE-T cells treated with the IMCnano eye drops for 30 min was 19.9% that of the accumulation from commercially available IMC eye drops. On the other hand, the corneal penetration of IMC from IMCnano eye drops was significantly greater than in the case of the commercially available IMC eye drops in both in vivo and in vitro studies using rabbit corneas. Taken together, we hypothesize that a nanoparticle formulation reduces the corneal toxicity of IMC eye drops, probably because the accumulation of IMC from IMCnano eye drops in the eye is lower than that from commercially available IMC eye drops. In addition, the nanoparticle formulation may allow a decrease in the amount of IMC used due to the increase in bioavailability, resulting in reduced drug toxicity. These findings provide significant information that can be used to design further studies aimed at developing less toxic eye drops.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
D-Mannitol, ≥98%
Sigma-Aldrich
Methyl cellulose, viscosity: 4,000 cP
Sigma-Aldrich
Indomethacin, 98.5-100.5% (in accordance with EP)
Supelco
Mannitol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Methyl cellulose, viscosity: 400 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 15 cP, BioReagent, suitable for cell culture
Sigma-Aldrich
Zirconium(IV) oxide, powder, 5 μm, 99% trace metals basis
Sigma-Aldrich
D-Mannitol, ACS reagent
Sigma-Aldrich
D-Mannitol, meets EP, FCC, USP testing specifications
Sigma-Aldrich
Methyl cellulose, viscosity: 1,500 cP
Sigma-Aldrich
D-Mannitol, BioXtra, ≥98% (HPLC)
Sigma-Aldrich
D-Mannitol, suitable for plant cell culture
Sigma-Aldrich
Zirconium(IV) oxide, nanopowder, <100 nm particle size (TEM)
Sigma-Aldrich
Methyl cellulose, viscosity: 15 cP
Sigma-Aldrich
Methocel® A4M, viscosity 3000-5500 mPa.s, 2 % in H2O(20 °C)
Sigma-Aldrich
Methocel® A15 LV, 27.5-31.5% methoxyl basis
Supelco
Indomethacin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Methyl cellulose, meets USP testing specifications, viscosity: 400 cP
Mannitol, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Zirconium, powder, −100 mesh
Millipore
D-Mannitol, ACS reagent, suitable for microbiology, ≥99.0%
USP
Mannitol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
D-Mannitol, BioUltra, ≥99.0% (sum of enantiomers, HPLC)
Sigma-Aldrich
Methyl cellulose, viscosity: 25 cP
Sigma-Aldrich
Indomethacin, meets USP testing specifications
Sigma-Aldrich
Methocel® A15C, medium viscosity, Methoxyl content 27.5-31.5 %
Sigma-Aldrich
D-Mannitol, tested according to Ph. Eur.
Sigma-Aldrich
Methyl cellulose, tested according to Ph. Eur.
Sigma-Aldrich
Zirconium, foil, thickness 0.1 mm, 99.98% trace metals basis
USP
Indomethacin, United States Pharmacopeia (USP) Reference Standard