Abstract

Co-delivery nanoparticles with characteristics of intracellular precision release drug have been generally accepted as an effective therapeutic strategy for eye diseases. In this study, we designed a new co-delivery system (miRNA/NP-BRZ) as a lasting therapeutic approach to prevent the neuro-destructive after the long-term treatment of glaucoma. Neuroprotective and intraocular pressure (IOP) response were assessed in in vivo and in vitro models of glaucoma. At the meaning time, we describe the preparation of miRNA/NP-BRZ, drug release characteristics, intraocular tracing, pharmacokinetic and pharmacodynamics study and toxicity test. We found that miRNA/NP-BRZ could remarkably decrease IOP and significantly prevent retinal ganglion cell (RGC) damages. The new formula of miRNA-124 encapsulated in PEG-PSA-BRZ nanoparticles exhibits high encapsulation efficiency (EE), drug-loading capacity (DC), and stable controlled-release efficacy (EC). Moreover, we also verified that the miRNA/NP-BRZ system is significantly neuroprotective and nontoxic as well as lowering IOP. This study shows our co-delivery drug system would have a wide potential on social and economic benefits for glaucoma.

摘要

具有细胞内精确释放药物特征的共递送纳米颗粒已被普遍接受为眼部疾病的有效治疗策略。在这项研究中，我们设计了一种新的共递送系统（miRNA / NP-BRZ）作为持久的治疗方法，以防止长期治疗青光眼后发生神经破坏。在体内和体外评估神经保护和眼内压（IOP）反应青光眼模型。在此意义上，我们描述了miRNA / NP-BRZ的制备，药物释放特征，眼内示踪，药代动力学和药效学研究以及毒性测试。我们发现，miRNA / NP-BRZ可以显着降低IOP并显着预防视网膜神经节细胞（RGC）损伤。包裹在PEG-PSA-BRZ纳米粒子中的miRNA-124的新配方表现出高的包裹效率（EE），载药量（DC）和稳定的控释功效（EC）。此外，我们还证实了miRNA / NP-BRZ系统具有明显的神经保护和无毒作用，并降低了IOP。这项研究表明，我们的共同给药药物系统在青光眼的社会和经济利益方面具有广阔的潜力。