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Development, implantation, in vivo elution, and retrieval of a biocompatible, sustained release subretinal drug delivery system

Authors

  • Nathan R.F. Beeley,

    1. Doheny Retina Institute, Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1450 San Pablo Street, Los Angeles, California 90033
    2. SurModics, Ophthalmology Division, 9924 West 74th Street, Eden Prairie, Minnesota 55344
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  • Jay M. Stewart,

    1. Doheny Retina Institute, Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1450 San Pablo Street, Los Angeles, California 90033
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  • Ryotaro Tano,

    1. Doheny Retina Institute, Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1450 San Pablo Street, Los Angeles, California 90033
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  • Laurie R. Lawin,

    1. SurModics, Ophthalmology Division, 9924 West 74th Street, Eden Prairie, Minnesota 55344
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  • Ralph A. Chappa,

    1. SurModics, Ophthalmology Division, 9924 West 74th Street, Eden Prairie, Minnesota 55344
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  • Guanting Qiu,

    1. Doheny Retina Institute, Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1450 San Pablo Street, Los Angeles, California 90033
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  • Aron B. Anderson,

    1. SurModics, Ophthalmology Division, 9924 West 74th Street, Eden Prairie, Minnesota 55344
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  • Eugene de Juan,

    1. Doheny Retina Institute, Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1450 San Pablo Street, Los Angeles, California 90033
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  • Signe E. Varner

    Corresponding author
    1. SurModics, Ophthalmology Division, 9924 West 74th Street, Eden Prairie, Minnesota 55344
    • SurModics, Ophthalmology Division, 9924 West 74th Street, Eden Prairie, Minnesota 55344
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Abstract

A biocompatible, sustained-release subretinal drug-delivery platform was developed to overcome the therapeutic accessibility limitations of current retinal disease treatments. The prototype implants were fabricated by coating nitinol, poly(methyl methacrylate) or chromic gut core filaments, with a drug-eluting polymer matrix. The polymer coatings are manufactured and coated by SurModics. The coating is a mixture of poly(butyl methacrylate) and poly(ethylene-co-vinyl acetate). The drug is either triamcinolone acetonide or sirolimus. The rods were successfully implanted into the subretinal space of 20/24 rabbits. Four rabbits were lost to early surgery from a dysfunctional infusion line and hemorrhage. No serious complications were observed during the 4-week follow-up period. Slight conjunctival redness was reported in all rabbits by 1-day follow-up, but the redness had subsided by the following week. Intraocular lens touch occurred in six rabbits during the implantations; of these, four had a lensectomy at the time of surgery, and the remaining two developed cataract. Corneal edema developed in three rabbits by 1-week follow-up, but subsided within 2 weeks. Initial observations of the implantation and elution characteristics revealed that the implants are well tolerated by the retinal tissue and that the implant can elute triamcinolone acetonide for a period of at least 4 weeks without eliciting an inflammatory response or complications. There were adverse clinical indications with the sirolimus-loaded implants at the delivered dose. Device retrieval required an uncomplicated surgical procedure, and revealed no associated or adherent tissue. Implant drug content analysis and opacity changes to the polymer matrix coating following retrieval demonstrated the sustained elution of the drug. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

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