A New Preparation Method for Ophthalmic Drug Nanoparticles

Nagai, Noriaki; Ito, Yoshimasa

doi:10.4172/2153-2435.1000305

Cited by 5 publications

(11 citation statements)

References 33 publications

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“…[6][7][8][9][10] The biodegradable polymer poly(DL-lactide-co-glycolide) (PLGA) has been widely utilized as a carrier for bioactive molecules and presents a possible solution to the limitations regarding ocular drug penetration (mean particle diameter, 50-200 nm). 6,7,[14][15][16][17][18] We have also reported the method of drug nanoparticles using the bead mill, [19][20][21][22][23][24][25] and showed that dispersions containing tranilast, indomethacin, or cilostazol nanoparticles enhanced corneal penetration as compared with traditional formulations (drug solutions type, eye drops). [20][21][22][23] We hypothesized that an ophthalmic formulation of DEX nanoparticles prepared using the bead mill method might offer high corneal permeability, and that enhancing transcorneal penetration of DEX would increase its effectiveness in treating ocular inflammation (as can occur in uveitis and after cataract surgery), and lead to an expansion of its usage as a therapy in the ophthalmologic field.…”

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“…Antimicrobial Activity of Ophthalmic Formulations Containing DEX The experiment was performed according to our previous reports using Escherichia coli (E. coli, ATC C 8739). 20) The E. coli (1 organism per aliquot) was incubated in the presence of saline containing 0.5% MC (MC solution); saline containing 0.026% MP and 0.014% PP (Paraben solution); MC solution plus 0.1% DEX nanoparticles (DEX nano without parabens); or DEX nano dispersion (with parabens) at 20 to 25°C. The data was represented as log colony-forming units (CFU) values.…”

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confidence: 99%

“…In Vitro Transcorneal Penetration of Ophthalmic Formulations Containing DEX The experiment was performed according to our previous reports using a methacrylate cell designed for transcorneal penetration studies. 20,22) The donor chamber exposed to the exterior surface of the cornea was filled with ophthalmic dispersion containing DEX. The reservoir chamber was filled with 10 mM 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid (HEPES) buffer (pH 7.4) containing 136.2 mM sodium chloride, 5.3 mM potassium chloride, 1.0 mM dipotassium phosphate, 1.7 mM calcium chloride and 5.5 mM glucose.…”

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confidence: 99%

“…where C DEX is the DEX concentration in DEX ophthalmic dispersion; τ is the lag time; δ is the thickness of the cornea (0.0625 cm); J c is the DEX penetration rate; K p is the penetration coefficient through the cornea; K m is the cornea/preparation partition coefficient; Q t is the total amount of DEX appearing in the reservoir solution at time t; A is the effective area of the cornea (0.78 cm 2 ); and D is the diffusion constant within the cornea. 20,22) In this study, the viability of the corneas was monitored by measurements of thickness or weight. In Vivo Transcorneal Penetration of Ophthalmic Formulations Containing DEX The experiment was performed according to the method reported previously by us.…”

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A Nanoparticle-Based Ophthalmic Formulation of Dexamethasone Enhances Corneal Permeability of the Drug and Prolongs Its Corneal Residence Time

Nagai

Nakazawa

Ito

et al. 2017

Biological & Pharmaceutical Bulletin

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We designed ophthalmic formulations containing dexamethasone-loaded solid nanoparticles (DEX dispersion), and investigated corneal permeability and toxicity. 0.1% dexamethasone (DEX) powder (DEX microparticles), 0.026% methyl p-hydroxybenzoate (MP), 0.014% propyl p-hydroxybenzoate (PP), and 0.5% methylcellulose were used, and the DEX dispersion was prepared by the bead mill method. The mean particle size of DEX dispersion was 78 nm. Antimicrobial activity of the DEX dispersion were measured by using Escherichia coli, and the corneal epithelium-debrided rat model and HCE-T cells (immortalized human corneal epithelial cell line) were used to estimate the corneal toxicity. The transcorneal penetration of the DEX dispersion were evaluated in the corneas of rabbit. The DEX dispersion was found to be highly stable until 14 d after its preparation. Although DEX itself did not exhibit antimicrobial activity, the DEX dispersion containing parabens (MP and PP) showed high antimicrobial activity, approximately equal to that of the solution containing parabens without DEX. The corneal penetration rate (J) and mean residence time (MRT) of DEX from the DEX dispersion were approximately 5.1- and 1.3-fold higher, respectively, than those of a dispersion containing DEX microparticles (mean particle size, 11.3 µm). In addition, no significant difference was found in corneal stimulation between the vehicle and DEX dispersion. In conclusion, we successfully prepared high quality dispersion containing DEX solid nanoparticles, and the nanoparticle-based ophthalmic formulation of DEX enhanced the corneal permeability and residence time of the drug. It is possible that DEX dispersion will show increased effectiveness in treating ocular inflammation.

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A Nanoparticle-Based Ophthalmic Formulation of Dexamethasone Enhances Corneal Permeability of the Drug and Prolongs Its Corneal Residence Time

Nagai

Nakazawa

Ito

et al. 2017

Biological & Pharmaceutical Bulletin

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“…5,9,11) We have prepared solid nanoparticles of such drugs as indomethacin, tranilast, cilostazol, and disulfiram (DSF), and reported that the abilities of these drugs to penetrate across the cornea can be significantly improved using solid nanoparticles. [12][13][14][15][16] It is expected that ophthalmic drug delivery systemsusingnanoparticlesmayprovidesufficientamountsof drugs into the lens.…”

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An Ophthalmic Formulation of Disulfiram Nanoparticles Prolongs Drug Residence Time in Lens

Nagai

Mano

Ito

2016

Biological & Pharmaceutical Bulletin

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Disulfiram (DSF) is a dimer of diethyldithiocarbamate (DDC) that we previously added to a solution of 2-hydroxypropyl-β-cyclodextrin (DSF solution). We found that the instillation of this DSF solution delayed lens opacification in a hereditary cataractous ICR/f rat. In this study, we attempted to design an ophthalmic formulation containing DSF nanoparticles for use as a lens targeted drug delivery system (nano-DSF suspension), and investigated the changes in drug content in the lens after the instillation of DSF solution or nano-DSF suspension. The nano-DSF suspension was prepared by a bead mill method to yield a mean particle size of nano-DSF of 181 nm. Following the instillation of 1.4% DSF solution or the nano-DSF suspension, DDC was detected only in the aqueous humor and lens; in both, the area under the curve (AUC) and mean residence time (MRT) for the nano-DSF suspension were higher than for the DSF solution. In addition, we found that the DDC residence time in the cortex and nucleus of the lens was higher than in the capsule-epithelium. Although DDC was not detected in the cortex and nucleus of lenses following the instillation of the 1.4% DSF solution, the instillation of a 1.4% nano-DSF suspension led to the accumulation of DDC in both areas. In conclusion, it is possible that the instillation of a nano-DSF suspension can supply more DDC into the aqueous humor and lens than a conventional formulation, and these findings provide information significant for the prevention of cataracts and the design of a lens targeted drug delivery system. Key words nanoparticle;lens;disulfiram;drugdeliverysystem;cataractCataracts are the leading cause of treatable blindness worldwide, and cataract surgery and intraocular drugs have been used as therapy. However, the availability of cataract surgery andintraoculardrugsisnotsufficientindevelopingcountries, and WHO has reported cataracts as the main cause of low vision in the many developing countries.1) Based on this background, the design and improvement of anti-cataract eye drops is very important.Eye drops comprise the major ophthalmic preparation, and their use is both convenient and safe. However, a high level of transcorneal penetration following the instillation of eye drops is necessary for drug delivery into the lens. Furthermore, the concentration of drugs administered as eye drops is dilutedtoapproximately20%bylacrimalfluids.2) In addition, the drops are lost from the tear film within 0.5-2min, with eye drop components excreted through the nasolacrimal duct into the mouth, 2) with a small amount remaining associated with the conjunctival tissue.2) Therefore, with traditional eye drops, only small amounts of the administered drug actually penetrate the cornea to reach the desired lens tissue due to corneal barriers and dilution caused by lacrimal fluids. 3-5)In an attempt to overcome these problems, several strategies have been devised using microparticles, viscous solutions and hydrogels. 3,[6][7][8][9][10] Recently, it has been reported that drug penetration ac...

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Nanomaterials for Treating Ocular Diseases

Vaidya

Sun

et al. 2016

Methods in Pharmacology and Toxicology

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A New Preparation Method for Ophthalmic Drug Nanoparticles

Cited by 5 publications

References 33 publications

A Nanoparticle-Based Ophthalmic Formulation of Dexamethasone Enhances Corneal Permeability of the Drug and Prolongs Its Corneal Residence Time

A Nanoparticle-Based Ophthalmic Formulation of Dexamethasone Enhances Corneal Permeability of the Drug and Prolongs Its Corneal Residence Time

An Ophthalmic Formulation of Disulfiram Nanoparticles Prolongs Drug Residence Time in Lens

Nanomaterials for Treating Ocular Diseases

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