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J. L. Lin, J. Lin, E. B. Lavik, S. Saluja, J. P. Bertram, J. C. Tsai, J. J. Huang; Controlled Sustained-Release of Biodegradable Intravitreal Methotrexate (MTX) Using Microparticle PLGA Polymer Technology. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5554.
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© ARVO (1962-2015); The Authors (2016-present)
To report dose and release-profile results for a novel, biodegradable intravitreal MTX coupled to a sustained-release PLGA polymer delivery system. This is the first report of a completely-biodegradable intravitreal MTX coupled to PLGA polymers for controlled drug-release within the eye.
This study examined the release of MTX from microspheres composed of Poly(D,L-lactic-co-glycolic acid; PLGA) and poly(D,L-lactic acid) (PLA). Three different sustained-release polymers (Resomer 502H, Resomer 503H, Resomer 502H-PLA blend) were tested to evaluate for MTX release-profiles. Using an in vivo rat model, intravitreal injections of MTX microspheres were injected into the eyes of Sprague Dawley rats. Intraocular fluid was collected at various timepoints and assayed for MTX concentrations.
All three tested sustained-release polymers containing MTX (Resomer 502H, Resomer 503H, Resomer 502H-PLA blend) showed peak release after 8 hours. Cumulative MTX released (µg/mg of polymer) for Resomer 502H, Resomer 503H, Resomer 502H-PLA blend were 1.082 ± 0.007, 0.754 ± 0.009, and 0.382 ± 0.007 respectively after 8 hours. After 14 days, cumulative MTX released (µg/mg of polymer) for Resomer 502H, Resomer 503H, Resomer 502H-PLA blend were 2.052 ± 0.195, 1.643 ± 0.0406, and 0.532 ± 0.0259 respectively.
These results show that a completely biodegradable MTX can be delivered in a dose-dependent and controlled manner using PLGA polymer technology as a sustained-release intravitreal drug-delivery vehicle. Biodegradable sustained-released intravitreal MTX would eliminate the need for repeated intravitreal injections to maintain intraocular drug levels or the need for implant removal as the case with other sustained-release delivery systems.An inflammatory cascade has been identified as a key pathway in ocular diseases such as uveitis, age-related macular degeneration, ocular lymphoma, and diabetic retinopathy. Thus, sustained-release intravitreal MTX potentially has many foreseeable applications. Further studies are needed to elucidate the potential of biodegradable intravitreal MTX drug delivery in these ocular conditions.
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