First Author: N.Takase JAPAN
Co Author(s): T. Yasukawa A. Kato H. Usui Y. Ogura
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Recently, the anti-vascular endothelial growth factor (anti-VEGF) therapy has been widely used to treat wet age-related macular degeneration, myopic choroidal neovascularization, and macular edema secondary to diabetic retinopathy and retinal vein occlusion. The anti-VEGF therapy, however, often requires repeated administration, burdenning patients mentally, physically and economically. To address this issue, a new drug release system may be necessary. The purpose of this study is to develop a new intraocular sustained drug delivery system applicable to bioactive proteins.
Nagoya City University Graduate School of Medical Sciences
As a prototype, an intraocular-lens-type hollow device filled with solid sodium fluorescein and C3F8 gas was prepared and implanted into rabbit eyes. Two 3-month-old white rabbits weighing approximately 2 kg were used. Under general anaesthesia, phacoemulsification of the lens was performed, following continuous curvilinear capsulorhexis in the same manner of cataract surgery. Then a device prepared was inserted into the capsular bag. Finally, the conjunctiva was sutured. After implantation, aqueous humor was periodically collected to measure concentrations of sodium fluorescein using a fluorophotometer. Gas remaining in the device was calculated from digital images of the anterior segment of the eye.
Aqueous humor was collected 1, 3, and 7 days and 1 and 2 months after surgery. In Rabbit 1, the concentration of sodium fluorescein was 197.5 µg/mL on the 1st postoperative day and ranged from 9.0 to 12.0 µg/mL from 3 days until 2 months after surgery. In Rabbit 2, the concentration of sodium fluorescein was 55.0 µg/mL on day 1 and 22.0 µg/mL on day 3, and ranged from 9.8 to 10.5 µg/mL on day 7 and later. In Rabbit 1, the percentage of residual C3F8 gas was approximately 8% in month 1 and 2% in month 2, while it was 42 and 31% in Rabbit 2, respectively.
The results of the current study suggested that a novel hollow-core device filled with long-lasting gas could provide sustained release of sodium fluorescein over 2 months. Filled gas preserved active pharmaceutical ingredients in a solid state in a device before release, potentially enabling sustained release of hydrophilic drugs involving anti-VEGF drugs. Further studies regarding material and design of a device and gas type are required to achieve more stable and longer drug release.