Co-Injection of Sulfotyrosine Facilitates Retinal Uptake of Hyaluronic Acid Nanospheres Following Intravitreal Injection.
Co-Injection of Sulfotyrosine Facilitates Retinal Uptake of Hyaluronic Acid Nanospheres Following Intravitreal Injection.
复制标题
DOI：
10.3390/pharmaceutics13091510
复制
发表时间：
2021-09-18
期刊：
影响因子：
5.4
通讯作者：
Naash MI
中科院分区：
文献类型：
--
作者：
Eblimit A;Makia MS;Strayve D;Crane R;Conley SM;Sinha T;Acharya G;Al-Ubaidi MR;Naash MI
基因和药物递送至视网膜是一个关键的治疗目标。虽然大多数遗传形式的视网膜变性影响外视网膜，特别是光感受器和视网膜色素上皮，但有效靶向递送至该区域需要侵入性视网膜下递送。我们在这项工作中的目标是评估两种创新方法，以提高所递送的纳米球的持久性及其对外视网膜的渗透，同时使用侵入性小得多的玻璃体内递送方法。我们配制了与荧光报告基因结合的新型透明质酸纳米球（HA-NS，直径 250 nm 和 500 nm），并将其玻璃体内递送至成年 Balb/C 小鼠视网膜。它们在玻璃体和内界膜 (ILM) 中表现出持久性长达 30 天（检测的最长时间点），但几乎没有视网膜渗透。因此，我们评估了小分子磺基酪氨酸破坏 ILM 的能力，发现 3.2 µg/μL 磺基酪氨酸可显着改善玻璃体内注射后向外视网膜的输送，而不会引起视网膜炎症、变性或功能丧失。磺基酪氨酸和HA-NS的共同递送导致HA-NS对视网膜的渗透以及沿着光感受器和视网膜色素上皮之间的界面的积累的显着改善。这些令人兴奋的发现表明，磺基酪氨酸和 HA-NS 可能是玻璃体内注射后外视网膜靶向的有效策略。
Gene and drug delivery to the retina is a critical therapeutic goal. While the majority of inherited forms of retinal degeneration affect the outer retina, specifically the photoreceptors and retinal pigment epithelium, effective targeted delivery to this region requires invasive subretinal delivery. Our goal in this work was to evaluate two innovative approaches for increasing both the persistence of delivered nanospheres and their penetration into the outer retina while using the much less invasive intravitreal delivery method. We formulated novel hyaluronic acid nanospheres (HA-NS, 250 nm and 500 nm in diameter) conjugated to fluorescent reporters and delivered them intravitreally to the adult Balb/C mouse retina. They exhibited persistence in the vitreous and along the inner limiting membrane (ILM) for up to 30 days (longest timepoint examined) but little retinal penetration. We thus evaluated the ability of the small molecule, sulfotyrosine, to disrupt the ILM, and found that 3.2 µg/µL sulfotyrosine led to significant improvement in delivery to the outer retina following intravitreal injections without causing retinal inflammation, degeneration, or loss of function. Co-delivery of sulfotyrosine and HA-NS led to robust improvements in penetration of HA-NS into the retina and accumulation along the interface between the photoreceptors and the retinal pigment epithelium. These exciting findings suggest that sulfotyrosine and HA-NS may be an effective strategy for outer retinal targeting after intravitreal injection.
登录
查看更多内容
影响因子：
4.3
作者：
Crane R;Conley SM;Al-Ubaidi MR;Naash MI
通讯作者：
Naash MI
影响因子：
4.4
作者：
Gauthier, R;Joly, S;Di Polo, A
通讯作者：
Di Polo, A
影响因子：
3.5
作者：
Eblimit, Aiden;Nguyen, Thanh-Minh T.;Chen, Rui
通讯作者：
Chen, Rui
影响因子：
4.8
作者：
Kelley, Ryan A.;Al-Ubaidi, Muayyad R.;Naash, Muna I.
通讯作者：
Naash, Muna I.
影响因子：
10.8
作者：
Ito, Tomoko;Iida-Tanaka, Naoko;Koyama, Yoshiyuki
通讯作者：
Koyama, Yoshiyuki