Schnichels Sven, Simmang David, Löscher Marina, Herrmann Andreas, de Vries Jan Willem, Spitzer Martin S, Hurst José
Centre for Ophthalmology, University Eye Hospital Tübingen, 72076 Tübingen, Germany.
DWI-Leibniz Institute for Interactive Materials, Forckenbeckstr. 50, 52056 Aachen, Germany.
Pharmaceutics. 2023 Feb 4;15(2):532. doi: 10.3390/pharmaceutics15020532.
Retinal eye diseases are the leading cause of blindness in the Western world. Up to date, the only efficient treatment for many retinal diseases consists of invasive intravitreal injections of highly concentrated drugs. Despite the fact that these injections are unpleasant for the patients, they potentially cause serious side effects, e.g., infections, bleeding within the eye or retinal detachment, especially when performed on a monthly basis, thus decreasing the injection frequency and lowering the desired drug dose. Therefore, a sustained released at the region of interest with a sustained release is desired. Recently, novel lipid-DNA nanoparticles (NPs) were shown to be an efficient drug delivery platform to the anterior segment of the eye. In this study, we investigated the distribution and tropism of the NPs when applied intravitreally, as a potential medication carrier to the posterior part of the eye. This technology is perfectly suited for the delivery of low molecular weight drugs to the back of the eye, which so far is greatly hindered by fast diffusion rates of the free drugs in the vitreous body and their intrinsically low retainability in ocular tissue. Excellent biodistribution, adherence and presence for up to five days was found for the different tested nanoparticles ex vivo and in vivo. In conclusion, our lipid-DNA based nanocarrier system was able to reach the retina within minutes and penetrate the retina providing potentially safe and long-term carrier systems for small molecules or nucleotide-based therapies.
视网膜眼部疾病是西方世界失明的主要原因。到目前为止，许多视网膜疾病唯一有效的治疗方法是通过侵入性玻璃体内注射高浓度药物。尽管这些注射对患者来说并不舒服，但它们可能会导致严重的副作用，例如感染、眼内出血或视网膜脱离，尤其是每月进行一次注射时，因此需要降低注射频率并减少所需的药物剂量。因此，人们期望在感兴趣的区域实现药物的持续释放。最近，新型脂质 - DNA纳米颗粒（NPs）被证明是一种有效的眼部前段药物递送平台。在本研究中，我们研究了玻璃体内注射NPs时它们的分布和靶向性，作为一种潜在的眼部后部药物载体。这项技术非常适合将低分子量药物递送至眼后部，而到目前为止，游离药物在玻璃体中的快速扩散速率以及它们在眼组织中固有的低滞留性极大地阻碍了这一过程。在体外和体内对不同测试纳米颗粒的研究发现，它们具有优异的生物分布、黏附性，并且能够在长达五天的时间内存在。总之，我们基于脂质 - DNA的纳米载体系统能够在数分钟内到达视网膜并穿透视网膜，为小分子或基于核苷酸的疗法提供了潜在安全且长期的载体系统。
