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Alina V. Dumitrescu, Kristyn Atkins, Andrew Shoffstall, Markus H. Kuehn, Young H. Kwon, Erin Lavik; Sustained Delivery of Timolol Reduces IOP, in Rabbits for Over 10 weeks. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3100.
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Poor compliance and ineffective delivery of topical drugs is a significant cause of failed medical treatment and disease progression in glaucoma. The availability of a sustained delivery vehicle that can be administered by the ophthalmologist could significantly improve care in certain patient populations.
Timolol maleate was encapsulated in polymer microspheres. Microspheres were delivered subconjunctivally by a single injection in New Zealand White rabbits. Aqueous humor, tears and blood samples were collected weekly. The IOP profile of rabbits was monitored using and the concentration of timolol was determined using HPLC/MS at 294 nm. Histochemical and immunohistochemical methods are used to evaluate whether injection of the microspheres elicited an inflammatory response in the anterior segment of rabbit eyes.
A single subconjunctival injection of this sustained-release formulation in rabbits resulted in significantly reduced IOP in animals injected with Timolol microspheres when compared to animals either injected with blank microspheres or untreated controls. IOP decreased in treated animals two weeks after injection and remained on average 25.6% lower (min = 18.0%; max=29.3%) than in control eyes for the entire duration of this trial (10 weeks). Timolol was detected in the aqueous humor for up to 9 weeks. Inflammation, infection, or other side effects was not observed in any injected eye and these findings were confirmed using histochemical and immunohistochemical methods. Timolol was undetectable in the serum (detection limit = 0.05 ng/ml).
Our data demonstrate that the subconjunctival injection of microspheres has the potential to deliver IOP lowering drugs to the aqueous humor for clinically relevant periods. Thus far our data indicate that this approach is effective and safe, without systemic or local side effects. This delivery system removes patient compliance issues and may be helpful for those who are unable to take topical medications consistently.
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