Overcoming the Anatomical and Physiological Barriers in Topical Eye Surface Medication Using a Peptide-Decorated Polymeric Micelle
Overcoming the Anatomical and Physiological Barriers in Topical Eye Surface Medication Using a Peptide-Decorated Polymeric Micelle
复制标题
使用肽修饰的聚合物胶束克服局部眼表药物中的解剖学和生理学障碍
DOI：
10.1021/acsami.9b13851
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发表时间：
2019-10-30
影响因子：
9.5
通讯作者：
Chen, Wei
中科院分区：
文献类型：
--
作者：
Lin, Sen;Ge, Chaoxiang;Chen, Wei
眼睛的密封解剖特征及其快速清除药物的生理活动被称为解剖和生理屏障，这是90%以上药物损失的原因。这方面仍然是眼表面药物治疗中的关键问题。因此，促进药物的组织渗透性以及延长其在眼表面上的保留可以提高其生物利用度并增强其治疗效果。由于眼表面存在带负电荷的粘蛋白层，制备了几种肽修饰的聚合物胶束，以增强胶束与眼表面之间的相互作用，从而延长药物在眼表面的保留并促进其组织渗透。他克莫司（也称为FK 506）是一种疏水性大环内酯类免疫抑制剂，用于治疗干眼综合征和其他眼科疾病。然而，其疏水性质使得其难以作为局部眼表面药物递送，并且由于过量而具有副作用的风险。因此，本工作的目的是评估FK 506胶束促进其在眼表面渗透性的能力。我们的研究结果表明，带正电荷的纳米胶束可以显着延长FK 506在眼表面的保留，并提高其在离体和体内条件下的角膜渗透性。FK506纳米胶束表现出比FK506悬浮液和商业FK506制剂上级的对干眼病的治疗效果。分别用滑动灯和转移酶介导的dUTP缺口末端标记法检测其对眼表炎症和角膜上皮细胞凋亡的抑制作用。进一步的分析表明，在mRNA和蛋白质水平上对几种炎症相关因子的表达具有更高的抑制作用。因此，我们的结果表明这些带正电的纳米胶束可能是眼表药物的良好药物递送系统。
The sealed anatomical features of the eye and its physiological activity that rapidly removes drugs are called anatomical and physiological barriers, which are the cause of more than 90% of drug loss. This aspect remains a critical issue in eye surface medication. Thus, promoting tissue permeability of drugs as well as prolonging their retention on the eye surface can improve their bioavailability and enhance their therapeutic effects. Thanks to the existence of a negatively charged mucin layer on the eye surface, several peptide-decorated polymeric micelles were prepared to enhance the interaction between the micelle and eye surface, thus prolonging the drug retention on the eye surface and promoting its tissue permeability. Tacrolimus (also known as FK506) is a hydrophobic macrolide immunosuppressant used to treat dry eye syndrome and other eye diseases. However, its hydrophobic nature makes its delivery as a topical eye surface medication difficult, with the risk of side effects due to overdoses. Therefore, the aim of this work is to evaluate the ability of FK506 micelles in promoting their permeability on the eye surface. Our results showed that the positively charged nanomicelles could significantly prolong FK506 retention on the eye surface and enhance its corneal permeability in ex vivo and in vivo conditions. FK506 nanomicelles exhibited superior curing effects against dry eye diseases than the FK506 suspension and a commercial FK506 formula. It exerted better inhibitory effects on eye surface inflammation and corneal epithelium apoptosis when examined by a slip lamp and a transferase-mediated dUTP nick end labeling assay, respectively. Further assays revealed the higher suppressive effects on the expression of several inflammation-related factors at an mRNA and protein level. Hence, our results suggested that these positively charged nanomicelles might be a good drug delivery system for ocular surface medication.