Centre for Ophthalmology, University Eye Hospital Tübingen, Elfriede-Aulhorn-Straße 7, Tübingen D-72076, Germany.
Clinic for Ophthalmology, University Medical Center Hamburg-Eppendorf (UKE), Martinistrasse 52, Hamburg D-20246, Germany.
ACS Appl Mater Interfaces. 2021 Mar 3;13(8):9445-9456. doi: 10.1021/acsami.0c18626. Epub 2021 Feb 2.
Glaucoma is the second leading cause of irreversible blindness worldwide. Among others, elevated intraocular pressure (IOP) is one of the hallmarks of the disease. Antiglaucoma drugs such as brimonidine can lower the IOP but their adherence to the ocular surface is low, leading to a low drug uptake. This results in a frequent dropping regime causing low compliance by the patients. Lipid DNA nanoparticles (NPs) have the intrinsic ability to bind to the ocular surface and can be loaded with different drugs. Here, we report DNA NPs functionalized for loading of brimonidine through specific aptamers and via hydrophobic interactions with double stranded micelles. Both NP systems exhibited improved affinity toward the cornea and retained release of the drug as compared to controls both in vitro and in vivo. Both NP types were able to lower the IOP in living animals significantly more than pristine brimonidine. Importantly, the brimonidine-loaded NPs showed no toxicity and improved efficacy and hence should improve compliance. In conclusion, this drug-delivery system offers high chances of an improved treatment for glaucoma and thus preserving vision in the aging population.
青光眼是全球第二大致盲原因。眼压升高（IOP）是该疾病的特征之一。像溴莫尼定这样的抗青光眼药物可以降低 IOP，但它们在眼表面的附着性低，导致药物摄取率低。这导致频繁滴眼，导致患者的依从性低。脂质 DNA 纳米颗粒（NPs）具有与眼表面结合的固有能力，并可以装载不同的药物。在这里，我们报告了通过特异性适体和与双链胶束的疏水相互作用来负载溴莫尼定的 DNA NPs。与对照相比，两种 NP 系统在体外和体内均表现出对角膜的亲和力提高，并且药物释放得到保留。两种 NP 类型都能够显著降低活体动物的眼压，比原始溴莫尼定效果更好。重要的是，负载溴莫尼定的 NPs 没有显示出毒性，并且提高了疗效，因此应该可以提高患者的依从性。总之，这种药物输送系统为改善青光眼治疗并因此保护老年人群的视力提供了很高的机会。
