Development of latanoprost-loaded biodegradable nanosheet as a new drug delivery system for glaucoma

Kenji Kashiwagi, Keisuke Ito, Hiroki Haniuda, Shinya Ohtsubo, Shinji Takeoka

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    Purpose. We investigated the IOP reduction and safety of latanoprost-loaded biodegradable nanosheet (LBNS) as a new antiglaucoma drug delivery system (DDS). Methods. We fabricated a 40 nm thick multilayered biodegradable nanosheet that is composed of chitosan and sodium alginate by means of the layer-by-layer method. Latanoprost isopropyl ester was loaded on the nanosheet to prepare 25, 2.5, and 0.25 μg/cm2 LBNSs. A nanosheet without latanoprost isopropyl ester (NS) and 0.005% latanoprost ophthalmic solution were prepared as controls. LBNSs or NS was applied to rat cornea, and IOP was monitored for 9 days. Local adverse effects and eye scratching movement also were investigated. The amount of latanoprost acid in aqueous humor and was measured in rabbits. Results. The 0.25 μg/cm2 LBNS and 0.005% latanoprost ophthalmic solution showed significant IOP reduction only for 1 day after application, whereas the IOP reduction rates of 2.5 μg/cm2 LBNS at 1, 2, 4, 7, and 9 days after application were -27.0% ± 14.8%, -22.0% ± 16.7%, -25.8% ± 18.0%, -22.7% ± 20.9%, and -6.6% ± 17.0%, respectively. The 25 μg/cm2 LBNS reduced IOP in a similar manner. The 25 μg/cm2 LBNS induced transient hyperemia, whereas the 0.25 and 2.5 μg/cm2 LBNSs did not exert any local adverse effects. The eye scratching movement test showed that application of 25 μg/cm2 LBNS did not cause any irritation of the eye. Latanoprost acid was detected in aqueous humor up to 6 days after application of 2.5 μg/cm2 LBNS. Conclusions. LBNS may be used as a novel antiglaucoma DDS.

    Original languageEnglish
    Pages (from-to)5629-5637
    Number of pages9
    JournalInvestigative Ophthalmology and Visual Science
    Volume54
    Issue number8
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    latanoprost
    Drug Delivery Systems
    Glaucoma
    Aqueous Humor
    Ophthalmic Solutions
    Eye Movements
    Esters
    Acids
    Hyperemia
    Chitosan
    Cornea

    Keywords

    • Chitosan
    • Drug delivery system
    • Glaucoma
    • Latanoprost
    • Nanosheet
    • Sodium alginate

    ASJC Scopus subject areas

    • Ophthalmology
    • Sensory Systems
    • Cellular and Molecular Neuroscience

    Cite this

    Development of latanoprost-loaded biodegradable nanosheet as a new drug delivery system for glaucoma. / Kashiwagi, Kenji; Ito, Keisuke; Haniuda, Hiroki; Ohtsubo, Shinya; Takeoka, Shinji.

    In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 8, 2013, p. 5629-5637.

    Research output: Contribution to journalArticle

    Kashiwagi, Kenji ; Ito, Keisuke ; Haniuda, Hiroki ; Ohtsubo, Shinya ; Takeoka, Shinji. / Development of latanoprost-loaded biodegradable nanosheet as a new drug delivery system for glaucoma. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 8. pp. 5629-5637.
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    abstract = "Purpose. We investigated the IOP reduction and safety of latanoprost-loaded biodegradable nanosheet (LBNS) as a new antiglaucoma drug delivery system (DDS). Methods. We fabricated a 40 nm thick multilayered biodegradable nanosheet that is composed of chitosan and sodium alginate by means of the layer-by-layer method. Latanoprost isopropyl ester was loaded on the nanosheet to prepare 25, 2.5, and 0.25 μg/cm2 LBNSs. A nanosheet without latanoprost isopropyl ester (NS) and 0.005{\%} latanoprost ophthalmic solution were prepared as controls. LBNSs or NS was applied to rat cornea, and IOP was monitored for 9 days. Local adverse effects and eye scratching movement also were investigated. The amount of latanoprost acid in aqueous humor and was measured in rabbits. Results. The 0.25 μg/cm2 LBNS and 0.005{\%} latanoprost ophthalmic solution showed significant IOP reduction only for 1 day after application, whereas the IOP reduction rates of 2.5 μg/cm2 LBNS at 1, 2, 4, 7, and 9 days after application were -27.0{\%} ± 14.8{\%}, -22.0{\%} ± 16.7{\%}, -25.8{\%} ± 18.0{\%}, -22.7{\%} ± 20.9{\%}, and -6.6{\%} ± 17.0{\%}, respectively. The 25 μg/cm2 LBNS reduced IOP in a similar manner. The 25 μg/cm2 LBNS induced transient hyperemia, whereas the 0.25 and 2.5 μg/cm2 LBNSs did not exert any local adverse effects. The eye scratching movement test showed that application of 25 μg/cm2 LBNS did not cause any irritation of the eye. Latanoprost acid was detected in aqueous humor up to 6 days after application of 2.5 μg/cm2 LBNS. Conclusions. LBNS may be used as a novel antiglaucoma DDS.",
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    author = "Kenji Kashiwagi and Keisuke Ito and Hiroki Haniuda and Shinya Ohtsubo and Shinji Takeoka",
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    AU - Kashiwagi, Kenji

    AU - Ito, Keisuke

    AU - Haniuda, Hiroki

    AU - Ohtsubo, Shinya

    AU - Takeoka, Shinji

    PY - 2013

    Y1 - 2013

    N2 - Purpose. We investigated the IOP reduction and safety of latanoprost-loaded biodegradable nanosheet (LBNS) as a new antiglaucoma drug delivery system (DDS). Methods. We fabricated a 40 nm thick multilayered biodegradable nanosheet that is composed of chitosan and sodium alginate by means of the layer-by-layer method. Latanoprost isopropyl ester was loaded on the nanosheet to prepare 25, 2.5, and 0.25 μg/cm2 LBNSs. A nanosheet without latanoprost isopropyl ester (NS) and 0.005% latanoprost ophthalmic solution were prepared as controls. LBNSs or NS was applied to rat cornea, and IOP was monitored for 9 days. Local adverse effects and eye scratching movement also were investigated. The amount of latanoprost acid in aqueous humor and was measured in rabbits. Results. The 0.25 μg/cm2 LBNS and 0.005% latanoprost ophthalmic solution showed significant IOP reduction only for 1 day after application, whereas the IOP reduction rates of 2.5 μg/cm2 LBNS at 1, 2, 4, 7, and 9 days after application were -27.0% ± 14.8%, -22.0% ± 16.7%, -25.8% ± 18.0%, -22.7% ± 20.9%, and -6.6% ± 17.0%, respectively. The 25 μg/cm2 LBNS reduced IOP in a similar manner. The 25 μg/cm2 LBNS induced transient hyperemia, whereas the 0.25 and 2.5 μg/cm2 LBNSs did not exert any local adverse effects. The eye scratching movement test showed that application of 25 μg/cm2 LBNS did not cause any irritation of the eye. Latanoprost acid was detected in aqueous humor up to 6 days after application of 2.5 μg/cm2 LBNS. Conclusions. LBNS may be used as a novel antiglaucoma DDS.

    AB - Purpose. We investigated the IOP reduction and safety of latanoprost-loaded biodegradable nanosheet (LBNS) as a new antiglaucoma drug delivery system (DDS). Methods. We fabricated a 40 nm thick multilayered biodegradable nanosheet that is composed of chitosan and sodium alginate by means of the layer-by-layer method. Latanoprost isopropyl ester was loaded on the nanosheet to prepare 25, 2.5, and 0.25 μg/cm2 LBNSs. A nanosheet without latanoprost isopropyl ester (NS) and 0.005% latanoprost ophthalmic solution were prepared as controls. LBNSs or NS was applied to rat cornea, and IOP was monitored for 9 days. Local adverse effects and eye scratching movement also were investigated. The amount of latanoprost acid in aqueous humor and was measured in rabbits. Results. The 0.25 μg/cm2 LBNS and 0.005% latanoprost ophthalmic solution showed significant IOP reduction only for 1 day after application, whereas the IOP reduction rates of 2.5 μg/cm2 LBNS at 1, 2, 4, 7, and 9 days after application were -27.0% ± 14.8%, -22.0% ± 16.7%, -25.8% ± 18.0%, -22.7% ± 20.9%, and -6.6% ± 17.0%, respectively. The 25 μg/cm2 LBNS reduced IOP in a similar manner. The 25 μg/cm2 LBNS induced transient hyperemia, whereas the 0.25 and 2.5 μg/cm2 LBNSs did not exert any local adverse effects. The eye scratching movement test showed that application of 25 μg/cm2 LBNS did not cause any irritation of the eye. Latanoprost acid was detected in aqueous humor up to 6 days after application of 2.5 μg/cm2 LBNS. Conclusions. LBNS may be used as a novel antiglaucoma DDS.

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    KW - Latanoprost

    KW - Nanosheet

    KW - Sodium alginate

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