Nathan R F Beeley

University of Southern California, Los Angeles, California, United States

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Publications (4)10.65 Total impact

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    ABSTRACT: To investigate the surgical feasibility and safety of a long-term intravitreal triamcinolone acetonide (TA) sustained delivery system. Pigmented rabbits were implanted with sustained-release formulations containing 925 microg of TA within a non-biodegradable polymer coating: Dose A (n = 15) with a slow delivery rate of 1 to 2 microg/day and Dose B (n = 15) releasing 3 to 5 microg/day. Additionally, a control group (n = 10) using a device coated with polymer only was implanted. The devices were surgically implanted through a 30-gauge sclerotomy into the vitreous cavity. The animals were clinically observed for up to 6 months after the surgery with complete ophthalmologic examinations. Histologic evaluation of a subset of eyes was performed at the conclusion of the study. Implants were successfully implanted in all 40 eyes. Ocular examinations revealed excellent implant tolerability. In all eyes, there was no significant postoperative inflammation at 1 week of follow-up. There was no increase in intraocular pressure during the follow-up period and histologic evaluation demonstrated no significant abnormalities. Minimal and localized vitreous hemorrhage was observed in 22.5% of implanted eyes and mostly cleared at 1 month after surgery. During the 6 months of follow up, localized lens opacities associated with physical implant contact developed in 66.6% of eyes. The surgical procedure using the intravitreal TA sustained delivery device is feasible. Surgical complications were generally mild, with lens opacities attributable to unique anatomical features of the rabbit eye. Long-term follow-up and histology revealed excellent implant tolerability.
    Ophthalmic Surgery Lasers and Imaging 03/2009; 40(2):160-8. DOI:10.3928/15428877-20090301-17 · 1.32 Impact Factor
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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
    Journal of Biomedical Materials Research Part A 03/2006; 76A(4):690 - 698. DOI:10.1002/jbm.a.30567 · 2.83 Impact Factor
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    ABSTRACT: A subretinal drug delivery system was developed to overcome the limitations of current treatments for retinal disease. A rod-shaped implant was made by embedding the corticosteroid triamcinolone acetonide within a biodegradable polycaprolactone polymer matrix. The implant was fabricated by homogeneously mixing the polymer and drug in solvent. The mixture was then dried, melted, and extruded, and the prepared solid form was drawn into a filament. The rods were mechanically sectioned to a length of 2 mm with a diameter of up to 320 microm. The rods were successfully implanted into the subretinal space of six rabbits. No complications were observed during the 4-week follow-up period. Initial observations of the implantation and elution characteristics revealed that polycaprolactone is well tolerated by the retinal tissue and that the implant can elute steroid for a period of at least 4 weeks without eliciting inflammatory response or complications. In vitro drug elution rates of different polymer to drug ratios and geometries into a balanced salt solution/bovine serum albumin (1%) solution showed an early rapid-release phase and late first-order phase. Histology and device retrieval after implantation revealed minimal encapsulation and good preservation of cellular morphology during the follow-up period and a more fibrous polymer microstructure of the implant.
    Journal of Biomedical Materials Research Part A 06/2005; 73(4):437-44. DOI:10.1002/jbm.a.30294 · 2.84 Impact Factor
  • Investigative Ophthalmology &amp Visual Science 01/2004; 45:U465. · 3.66 Impact Factor