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

Journal Article · 29 November 2018 · ACS Central Science

DOI: https://doi.org/10.1021/acscentsci.8b00641 · OSTI ID:1571944

Mu, Changhua ^[1]; Shi, Meng ^[2]; Liu, Ping ^[3]; Chen, Lu ^[4]; Marriott, Gerard  ^[1]

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1. Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering, and Tsinghua-Berkeley Shenzhen Inst.
2. Univ. of California, Berkeley, CA (United States). Vision Science Graduate Program and School of Optometry
3. Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering
4. Univ. of California, Berkeley, CA (United States). Tsinghua-Berkeley Shenzhen Inst., and Vision Science Graduate Program and School of Optometry

Timolol, a potent inhibitor of β-adrenergic receptors (βARs), 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 × 10⁷ times the inhibitory concentration (k_i) for βARs. 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 k_i). 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 βARs over a 10 h period. Second, the contact lenses inhibit βARs 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 βARs. Fourth, our lenses are disposable, designed for single day use, and manufactured at a low cost.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC)
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 1571944
• Journal Information: ACS Central Science, Journal Name: ACS Central Science Journal Issue: 12 Vol. 4; ISSN 2374-7943
• Publisher: American Chemical Society (ACS)Copyright Statement
• Country of Publication: United States
• Language: English