Daylight-Mediated, Passive, and Sustained Release of the Glaucoma Drug Timolol from a Contact Lens [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 006.7 Multimedia systems

Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2018

Mô tả vật lý: Size: p. 1677-1687 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 261885

 Timolol, a potent inhibitor of ?-adrenergic receptors (?ARs), is a first-line drug for decreasing the intraocular pressure (IOP) of patients with glaucoma. Timolol is administered using 0.5% eye-drop solutions at >
 3 � 10<
 sup>
 7<
 /sup>
  times the inhibitory concentration (<
 em>
 k<
 sub>
 i<
 /sub>
 <
 /em>
 ) for ?ARs. This high dose is wasteful and triggers off-target effects that increase medication noncompliance. Here, we introduce contact lenses that release timolol to the eye throughout the day during passive exposures to natural daylight at a more therapeutically relevant concentration (>
 3000 <
 em>
 k<
 sub>
 i<
 /sub>
 <
 /em>
 ). Timolol is coupled to the polymer of the contact lens via a photocleavable caged cross-linker and is released exclusively to the surrounding fluid after the 400-430 nm mediated cleavage of the cross-linking group. Studies conducted in a preclinical mouse model of glaucoma show photoreleased timolol is effective as authentic timolol in reducing IOP. Our studies highlight several advantages of daylight-mediated release of timolol from lenses compared to eye-drops. First, fitted contact lenses exposed to natural daylight release sufficient timolol to sustain the inhibition of ?ARs over a 10 h period. Second, the contact lenses inhibit ?ARs in the eye using only 5.7% of the timolol within a single eye-drop. Third, the lenses allow the patient to passively control the amount of timolol released from the lens-for example, early morning exposure to outdoor sunlight would release enough timolol to maximally reduce the IOP, whereas subsequent periodic exposures to indoor daylight would release sufficient timolol to overcome the effects of its spontaneous dissociation from ?ARs. Fourth, our lenses are disposable, designed for single day use, and manufactured at a low cost.
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