Departamento de Farmacología, Centro de Investigación Y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de Mexico, Mexico.
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico.
J Nanobiotechnology. 2022 Sep 15;20(1):413. doi: 10.1186/s12951-022-01612-5.
Parkinson's disease (PD) significantly affects patients' quality of life and represents a high economic burden for health systems. Given the lack of safe and effective treatments for PD, drug repositioning seeks to offer new medication alternatives, reducing research time and costs compared to the traditional drug development strategy. This review aimed to collect evidence of drugs proposed as candidates to be reused in PD and identify those with the potential to be reformulated into nanocarriers to optimize future repositioning trials. We conducted a detailed search in PubMed, Web of Science, and Scopus from January 2015 at the end of 2021, with the descriptors "Parkinson's disease" and "drug repositioning" or "drug repurposing". We identified 28 drugs as potential candidates, and six of them were found in repositioning clinical trials for PD. However, a limitation of many of these drugs to achieve therapeutic success is their inability to cross the blood-brain barrier (BBB), as is the case with nilotinib, which has shown promising outcomes in clinical trials. We suggest reformulating these drugs in biodegradable nanoparticles (NPs) based on lipids and polymers to perform future trials. As a complementary strategy, we propose functionalizing the NPs surface by adding materials to the surface layer. Among other advantages, functionalization can promote efficient crossing through the BBB and improve the affinity of NPs towards certain brain regions. The main parameters to consider for the design of NPs targeting the central nervous system are highlighted, such as size, PDI, morphology, drug load, and Z potential. Finally, current advances in the use of NPs for Parkinson's disease are cited.
帕金森病（PD）显著影响患者的生活质量，对医疗系统造成巨大的经济负担。鉴于目前缺乏安全有效的 PD 治疗方法，药物重定位旨在提供新的药物选择，与传统药物开发策略相比，可减少研究时间和成本。本综述旨在收集用于 PD 的重定位候选药物的证据，并确定那些有可能被重新配方制成纳米载体以优化未来重定位试验的药物。我们在 PubMed、Web of Science 和 Scopus 上进行了详细的检索，检索时间为 2015 年 1 月至 2021 年底，检索词为“Parkinson's disease”和“drug repositioning”或“drug repurposing”。我们确定了 28 种作为潜在候选药物的药物，其中 6 种药物正在进行 PD 的重定位临床试验。然而，许多药物无法穿过血脑屏障（BBB），这是它们无法达到治疗成功的限制因素之一，nilotinib 就是这种情况，它在临床试验中显示出了有希望的结果。我们建议将这些药物重新配方制成基于脂质和聚合物的可生物降解纳米颗粒（NPs），以进行未来的试验。作为一种补充策略，我们建议通过向表面层添加材料来对 NPs 表面进行功能化。除其他优点外，功能化可以促进高效穿越 BBB，并提高 NPs 对某些大脑区域的亲和力。突出了设计针对中枢神经系统的 NPs 的主要参数，例如尺寸、PDI、形态、药物载量和 Z 电位。最后，引用了目前在帕金森病中使用 NPs 的进展。
