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    2015 ARVO finds connections in innovative drug delivery, therapies

    Cutting-edge progress also continues in retina, cornea, dry eye, gene-based science

     

    More extensive device engineering was demonstrated in a “nanowafer” drug delivery system, tested in a model of corneal neovascularization (Acharya G. IOVS. 2015;56:ARVO E-Abstract 5032). The nanowafer—composed of a transparent circular disc that contains arrays of drug-loaded nanoreservoirs—is placed on the ocular surface. For this study, the tyrosine kinase inhibitor, axitinib (Inlyta, Pfizer), an FDA-approved treatment for renal cell carcinoma, was used as a test therapy. One-daily nanowafer was significantly more efficacious than twice-daily eye drop treatments of axitinib.

    Other studies of drug delivery paradigms focused on slow-release depot forms of vascular endothelial growth factor (VEGF) inhibitors. Initial in vitro pharmacokinetic work is being done on controlled-release polymer reservoirs (Abe T. IOVS. 2015;56:ARVO E-Abstract 4146) and a polymer nanoparticle system was described in which conjugation of bevacizumab (Avastin, Genentech) was shown to reduce leakage of the drug into the bloodstream (Kong L. IOVS. 2015 56:ARVO E-Abstract 5029). This prolonged its retention in the vitreous, making it potentially safer and more effective by reducing systemic exposure and extending ocular residence time.

    A number of studies examining properties of bevacizumab-packaged microparticles were also presented, including pharmacokinetic studies of microparticles within sustained-release hydrogel matrices (Tully S. IOVS. 2015;56:ARVO E-Abstract 222; Owens G. IOVS. 2015;56:ARVO E-Abstract 236; Verhoeven RS. IOVS. 2015;56:ARVO E-Abstract 230).

    If this year’s presentations are any indication, a major focus of retinal therapies in the near future will be the refinement of these many therapeutic delivery options.

    More retina

    Improving the treatment options and visual outcomes for patients with retinal diseases—including age-related macular degeneration (AMD)—was not just about drug delivery, however. While monoclonal antibody inhibitors of VEGF have provided a valuable treatment option for many patients with AMD, variable responses and the necessity of once- or twice-monthly intravitreal injections provide a continuous pressure to develop new treatment regimes.

    One approach involves a system of de novo-designed, cell-penetrating peptide constructs fused to a therapeutic protein transduction domain (DeCogan F. IOVS. 2015;56:ARVO E-Abstract 4147). This system was shown to transport µg quantities of macromolecules, such as very large monoclonal VEGF inhibitors, in a topical eyedrop that enables penetration to the posterior segment.

    Another area of interest is small-molecule therapies that can avoid the problems of penetration and absorption of the macromolecule monoclonal VEGF inhibitors. Initial in vitro screens included inhibitors of the P13K/Akt/mTOR pathway (Sasore T. IOVS. 2015;56:ARVO E-Abstract 2305) and iso-quinolone sulfonamide derivatives that inhibit protein kinase function (Sugimoto M. IOVS. 2015;56:ARVO E-Abstract 150). Pharmacokinetics and initial vascular leakage models were used to assess the ability of mucus-penetrating particles to deliver drug (in this case, a tyrosine kinase inhibitor) in topical formulations to the back of the eye (Schopf L. IOVS. 2015;56:ARVO E-Abstract 2279).

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