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Saffar Mansoor, Samikrumar R. Patel, Cetin Tas, Rashmi Pacha-Ravi, Uday B. Kompella, Henry F. Edelhauser, Mark R. Prausnitz; Pharmacokinetics and Biodistribution of Bevacizumab Following Suprachoroidal Injection into the Rabbit Eye Using a Microneedle. Invest. Ophthalmol. Vis. Sci. 2012;53(14):498.
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As an alternative to intravitreal injection, this study presents injection of bevacizumab into the suprachoroidal space (SCS) using a hollow microneedle. This minimally invasive approach deposits bevacizumab between the sclera and choroid, which targets drug delivery to its therapeutic site of action. The purpose of this study is to quantify the pharmacokinetics and biodistribution of bevacizumab in the rabbit eye. This is the first study to assess bevacizumab delivery in vivo after injection into the SCS using a microneedle.
Bevacizumab (Avastin®, 1250 µg/50 µl) was injected into the SCS of pigmented rabbits using a metal microneedle measuring 700-800 µm in length inserted 5 mm posterior to the limbus. Rabbits were euthanatized and eyes were enucleated at 15 min, 1 day, and 2 days following SCS injection. Ocular tissues (sclera, choroid, retina, aqueous humor, vitreous, anterior tissues, lens and optic nerve) were separated. Bevacizumab was then extracted from these tissues and quantified using ELISA.
The percent bevacizumab recovered from the eyes was 88.4±0.9% at 15 min, 4.6±0.5% at 1 day, and 0.2±0.1% at 2 days after injection. The distribution of bevacizum in ocular tissues at 15 min after injection was 76% in choroid, 13% in sclera and 2.9% in retina, 1.0% in vitreous, 0.5% in aqueous humor, 0.9% in anterior chamber, 0.6% in lens and 0.1% in optic nerve. After 1 day, drug levels were 34% in choroid, 27% in sclera and 23% in retina, 11% in vitreous, 0.7% in aqueous humor, 1.6% in anterior chamber, 3.8% in lens and 0.3% in optic nerve. After 2 days, the distribution of bavacizum was 0.5% in choroid, 3.3% in sclera, 0.5% in retina, 55% in vitreous, 3% in aqueous humor, 36% in anterior chamber, 1.1% in lens and 0.6% in optic nerve.
A microneedle was able to inject bevacizumab into the SCS of rabbit eyes using a minimally invasive procedure. There was a quick biodistribution of bevacizumab into choroid, sclera, and retina, indicating excellent drug targeting. However, choroidal levels of bevacizumab declined very rapidly. The current formulation of bevacizumab is therefore not optimal and a sustained-release formulation of bevacizumab may be needed to achieve sustained delivery to the posterior segment of the eye.
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