Intrascleral Drug Delivery to the Eye Using Hollow Microneedles
Intrascleral Drug Delivery to the Eye Using Hollow Microneedles
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DOI：
10.1007/s11095-008-9756-3
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发表时间：
2009-02-01
影响因子：
3.7
通讯作者：
Prausnitz, Mark R.
中科院分区：
文献类型：
--
作者：
Jiang, Jason;Moore, Jason S.;Prausnitz, Mark R.
目的.本研究验证了中空微针可以以微创方式将含有可溶性分子、纳米颗粒和微粒的溶液注入巩膜的假设。将单独的中空微针插入人尸体巩膜中，但不穿过人尸体巩膜，并将含有磺酰罗丹明或荧光标记的纳米颗粒或微粒的水溶液在恒定压力下输注到巩膜中。测量液体的注入量并进行组织学成像，作为巩膜厚度、注入压力、针头缩回深度和扩散酶（透明质酸酶和胶原酶）存在的函数。单个中空微针能够插入巩膜中。在微针插入巩膜而不缩回之后，流体输注极其缓慢，但是微针在200-300 μ m的距离上的部分缩回使得能够将10-35 μ l流体输注到组织中。巩膜厚度和输液压力对液体输送的影响不显著。纳米颗粒悬浮液也可进入巩膜，但微粒仅在透明质酸酶和胶原酶扩散酶存在下进入巩膜，这表明巩膜糖胺聚糖和胶原纤维作为限速屏障的作用。该研究表明，中空微针可以将溶液注入巩膜中，用于可溶性分子、纳米颗粒和微粒的微创递送。
Purpose. This study tested the hypothesis that hollow microneedles can infuse solutions containing soluble molecules, nanoparticles, and microparticles into sclera in a minimally invasive manner.Methods. Individual hollow microneedles were inserted into, but not across, human cadaver sclera and aqueous solutions containing sulforhodamine or fluorescently tagged nanoparticles or microparticles were infused into sclera at constant pressure. The infused volume of fluid was measured and imaged histologically as a function of scleral thickness, infusion pressure, needle retraction depth and the presence of spreading enzymes (hyaluronidase and collagenase).Results. Individual hollow microneedles were able to insert into sclera. Fluid infusion was extremely slow after microneedle insertion into the sclera without retraction, but partial retraction of the microneedle over a distance of 200-300 mu m enabled infusion of 10-35 mu l of fluid into the tissue. Scleral thickness and infusion pressure had insignificant effects on fluid delivery. Nanoparticle suspensions were also delivered into sclera, but microparticles were delivered only in the presence of hyaluronidase and collagenase spreading enzymes, which suggested the role of scleral glycosaminoglycans and collagen fibers as rate-limiting barriers.Conclusion. This study shows that hollow microneedles can infuse solutions into the sclera for minimally invasive delivery of soluble molecules, nanoparticles and microparticles.