Efficient and noninvasive drug delivery for glaucoma therapy necessitates prolonged retention on the ocular surface and deep penetration into the cornea. However, inherent physiological defenses such as rapid tear clearance and low cornea permeability present significant challenges that hinder the effectiveness of trans-corneal drug delivery. In this study, we demonstrate the potential of zwitterionic micelles composed of poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)-block-poly(ε-caprolactone) (OPDEA-PCL) amphiphiles as a biocompatible carrier for trans-corneal drug delivery. These micelles exhibit enhanced adhesion to ocular tissues and resistance to tear clearance due to their unique affinity for cell membranes. These characteristics facilitate adsorptive-mediated transcytosis, significantly augmenting trans-corneal transport and intraocular accumulation of the glaucoma medication brinzolamide (BRZ). As a result, OPDEA-PCL/BRZ formulations effectively normalize intraocular pressure in an open-angle glaucoma rat model, surpassing PEGylated and free BRZ formulations. This research underscores the potential utility of OPDEA-PCL micelles as a promising vehicle for noninvasive topical trans-corneal drug delivery in glaucoma therapy.

中文翻译：

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使用眼部粘胶束进行主动经角膜药物递送，用于高效青光眼治疗


用于青光眼治疗的高效和无创药物输送需要长时间保留在眼表并深入渗透到角膜中。然而，固有的生理防御（如快速泪液清除和低角膜通透性）带来了阻碍经角膜药物输送效果的重大挑战。在这项研究中，我们展示了由聚（2-（N-氧化物-N，N-二乙氨基）甲基丙烯酸乙酯）-嵌段-聚（ε-己内酯）（OPDEA-PCL）两亲物组成的两性离子胶束作为经角膜药物递送的生物相容性载体的潜力。由于这些胶束对细胞膜的独特亲和力，它们表现出增强的对眼组织的粘附性和抗撕裂清除能力。这些特性促进了吸附介导的转胞吞作用，显着增强了青光眼药物布林佐胺 （BRZ） 的跨角膜转运和眼内蓄积。因此，OPDEA-PCL/BRZ 制剂有效地使开角型青光眼大鼠模型中的眼压正常化，超过了聚乙二醇化和游离 BRZ 制剂。这项研究强调了 OPDEA-PCL 胶束作为青光眼治疗中无创局部经角膜药物递送的有前途的载体的潜在用途。