Coated microneedles for drug delivery to the eye
Coated microneedles for drug delivery to the eye
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DOI：
10.1167/iovs.07-0066
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发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Prausnitz, Mark R.
中科院分区：
文献类型：
--
作者：
Jiang, Jason;Gill, Harvinder S.;Prausnitz, Mark R.
目的。为了验证包被微针可以通过巩膜内和角膜内途径以微创方式将药物输送到眼睛中的假设。长度为500 ~ 750 μ m的固体金属微针被模型药物、蛋白质和DNA包裹；插入未保存的人体尸体巩膜；和成像。将荧光素钠包被的微针植入兔角膜内。取针后，测定兔眼前段荧光素浓度24小时。用皮罗卡品包被微针进行类似实验，并监测兔瞳孔大小。体外插入试验表明，微针的机械强度足以穿透人体巩膜，并且药物涂层在插入后30秒内迅速从巩膜组织中溶解。荧光素包被微针的体内给药表明，前房的荧光素浓度比不使用微针的局部应用高60倍。同样，微针给药匹罗卡品引起兔瞳孔迅速和广泛收缩。微针插入未引起可测量的炎症反应。这项研究首次证明了涂层微针可以通过巩膜内和角膜内途径将药物输送到眼睛中。这种微创入路可避免眼内注射和全身给药的并发症。
PURPOSE. To test the hypothesis that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes in a minimally invasive manner.METHODS. Solid metal microneedles measuring 500 to 750 mu m in length were coated with model drugs, protein, and DNA; inserted into nonpreserved human cadaveric sclera; and imaged. Microneedles coated with sodium fluorescein were then inserted into rabbit cornea in vivo. After needle removal, fluorescein concentration in the anterior segment of the rabbit eye was measured for 24 hours. Similar experiments were performed using pilocarpine-coated microneedles, and the rabbit pupil size was monitored afterward.RESULTS. In vitro insertion tests showed that microneedles were mechanically strong enough to penetrate into human cadaveric sclera and that the drug coating rapidly dissolved off the needles within the scleral tissue within 30 seconds after insertion. In vivo delivery from fluorescein-coated microneedles showed that fluorescein concentrations in the anterior chamber were 60 times greater than those achieved by topical application without microneedles. Similarly, microneedle delivery of pilocarpine caused rapid and extensive rabbit pupil constriction. There were no measurable inflammatory responses caused by microneedle insertion.CONCLUSIONS. This study demonstrated for the first time that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes. This minimally invasive approach may avoid the complications associated with intraocular injection and systemic administration.