Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA.
J Control Release. 2023 Oct;362:371-380. doi: 10.1016/j.jconrel.2023.08.058. Epub 2023 Sep 4.
Effective eye drop delivery systems for treating diseases of the posterior segment have yet to be clinically validated. Further, adherence to eye drop regimens is often problematic due to the difficulty and inconvenience of repetitive dosing. Here, we describe a strategy for topically dosing a peptide-drug conjugate to achieve effective and sustained therapeutic sunitinib concentrations to protect retinal ganglion cells (RGCs) in a rat model of optic nerve injury. We combined two promising delivery technologies, namely, a hypotonic gel-forming eye drop delivery system, and an engineered melanin binding and cell-penetrating peptide that sustains intraocular drug residence time. We found that once daily topical dosing of HR97-SunitiGel provided up to 2 weeks of neuroprotection after the last dose, effectively doubling the therapeutic window observed with SunitiGel. For chronic ocular diseases affecting the posterior segment, the convenience of an eye drop combined with intermittent dosing frequency could result in greater patient adherence, and thus, improved disease management.
尚未对用于治疗后节疾病的有效滴眼剂输送系统进行临床验证。此外，由于重复给药的难度和不便，滴眼剂方案的依从性往往存在问题。在这里，我们描述了一种局部给予肽药物偶联物的策略，以实现有效的和持续的治疗性舒尼替尼浓度，从而在视神经损伤的大鼠模型中保护视网膜神经节细胞（RGC）。我们结合了两种有前途的输送技术，即低渗凝胶形成滴眼剂输送系统和一种工程化的黑色素结合和细胞穿透肽，可维持眼内药物滞留时间。我们发现，HR97-SunitiGel 每日一次局部给药，可在最后一次给药后提供长达 2 周的神经保护作用，与 SunitiGel 相比，有效延长了治疗窗口。对于影响后节的慢性眼部疾病，滴眼剂的便利性和间歇性给药频率可能会导致更高的患者依从性，从而改善疾病管理。
