Department of Chemical and Environmental Technology, Rey Juan Carlos University, C/Tulipán s/n, 28933, Móstoles, Madrid, Spain.
Department of Chemical & Process Engineering, University of Strathclyde, Glasgow G1 1XJ, UK.
J Mater Chem B. 2021 May 26;9(20):4178-4189. doi: 10.1039/d1tb00481f.
Parkinson's disease (PD) is a progressive neurodegenerative disease, the 2nd most common after Alzheimer's disease, the main effect of which is the loss of dopaminergic neurons. Levodopa or l-Dopa is an amino acid used in the treatment of PD that acts as the immediate precursor to dopamine. However, over time the efficacy of the medication gradually decreases requiring modified delivery methods. One of the major challenges for the medication to work is to achieve a gradual continuous supply of l-Dopa to the brain to minimise symptoms. Herein, mesoporous silica nanoparticles (MSNs) were engineered through the concept of drug-structure-directing agents (DSDAs) with inherent therapeutic activity. The DSDA used was l-Dopa drug modified by amidation with fatty acids to build anionic surfactants that were able to form micelles as templates for the assembly of inorganic precursors to form the silica framework. This templating route produced MSNs with tunable sizes ranging from 100 nm to 1 μm and with different shapes: spherical, with either solid structures with radial mesopores and porous shells, or hollow-shells with inside large void cavities; and elongated, characterized by long hollows covered by mesoporous shells. The concept of using DSDAs to synthesize drug nanocarriers can be used to avoid the surfactant removal and subsequent drug loading steps involved in the synthesis of conventional MSNs. We hypothesized that the l-Dopa released from MSN materials is mediated by the size and solubility of the DSDAs, and the surface chemical interactions between the DSDAs and MSN hosts. Different pHs (acidic and neutral) simulating gastrointestinal tract conditions were tested, and the results showed hardly any release for gastric conditions at pH 1.2, avoiding the premature release in the stomach typical of conventional MSNs, while for intestinal conditions of pH 7.4, the release of l-Dopa occurred in a continuous and sustained manner, which is well suited to the drug's application and delivery route, and matches well with achieving a sustained l-Dopa delivery to relief symptoms. This could open up new uses for MSNs synthesized by this approach to treat PD.
帕金森病（PD）是一种进行性神经退行性疾病，仅次于阿尔茨海默病，其主要影响是多巴胺能神经元的丧失。左旋多巴或 l-多巴是一种用于治疗 PD 的氨基酸，作为多巴胺的直接前体。然而，随着时间的推移，药物的疗效逐渐下降，需要改进给药方法。药物发挥作用的主要挑战之一是实现向大脑的逐渐连续供应 l-多巴，以最大限度地减少症状。在此，通过药物结构导向剂（DSDA）的概念，设计了介孔硅纳米粒子（MSNs），其具有内在的治疗活性。使用的 DSDA 是通过与脂肪酸酰胺化修饰的 l-多巴药物，形成阴离子表面活性剂，能够形成胶束作为无机前体组装的模板，形成硅骨架。这种模板路线生产的 MSNs 具有可调节的尺寸范围从 100nm 到 1μm，并且具有不同的形状：球形，具有带有径向介孔和多孔壳的实心结构，或具有内部大空腔的空心壳；和拉长的，其特征在于由介孔壳覆盖的长空心。使用 DSDAs 合成药物纳米载体的概念可以避免在合成传统 MSNs 时涉及的表面活性剂去除和随后的药物负载步骤。我们假设从 MSN 材料中释放的 l-多巴是由 DSDAs 的尺寸和溶解度以及 DSDAs 和 MSN 宿主之间的表面化学相互作用介导的。测试了不同的 pH 值（酸性和中性）模拟胃肠道条件，结果表明在 pH 1.2 的胃条件下几乎没有释放，避免了传统 MSNs 中典型的胃中过早释放，而在 pH 7.4 的肠道条件下，l-多巴的释放以连续和持续的方式发生，这非常适合药物的应用和给药途径，并且与实现持续的 l-多巴递送以缓解症状非常吻合。这可能为通过这种方法合成的 MSNs 开辟新的用途，用于治疗 PD。
