Lorenzoni Ricardo, Davies Samuel, Cordenonsi Leticia Malgarim, Viçosa José Alcides da Silva, Mezzomo Nathana Jamille, de Oliveira Amanda Lima, Carmo Guilherme Machado do, Raffin Renata Platcheck, Alves Oswaldo Luiz, Vaucher Rodrigo De Almeida, Rech Virginia Cielo
Programa de Pós-Graduação em Nanociências, Universidade Franciscana CP, 97010-030, Santa Maria, RS, Brazil; CNC-Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra CP, 3004-517, Coimbra, Portugal.
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul CP, 90610-000, Porto Alegre, RS.
Eur J Pharm Sci. 2020 Aug 1;151:105397. doi: 10.1016/j.ejps.2020.105397. Epub 2020 May 30.
The development of cognitive impairment may be related to high levels of plasma cholesterol and obesity. Simvastatin (SV) and lovastatin (LV) are drugs that can potentially be used for the treatment of cognitive deficit. This study aimed to develop and characterize lipid-core nanocapsules (LNC) containing SV (SV-LNC) or LV (LV-LNC), evaluating the effects of SV-LNC in an animal model of cognitive deficit. The formulations SV-LNC and LV-LNC presented a particle average size around 200 nm, a low-polydispersity index, and negative zeta potential. Analysis of differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy showed that there is no reaction among LNC components: LV was crystallized in the suspensions, and SV was molecularly dispersed. The encapsulation efficiency of the SV was high (98.9 ± 1.4%), while that of the LV was low (21.5 ± 1.5%).Based on these results, SV-LNC was used in the preclinical studies. Animals fed with a hyperlipidic diet (HD) developed obesity, hypercholesterolemia, and cognitive impairment, which was corroborated by the brain lesions indicated by histological analysis of some of the animals that received the high-fat diet. We observed that free simvastatin (CS3) was able to reduce the enzymatic activity of pyruvate kinase, an important enzyme for brain energy homeostasis, without affecting the memory of the animals that received a standard diet. However, it failed to improve the cognitive damage caused by a diet high in cholesterol and saturated fats. On the other hand, when simvastatin is "camouflaged" in the lipid-core nanocapsules (HNS3), this cognitive impairment improves. Thus, SV-LNC is a promising alternative therapy for the treatment of cognitive impairment.
认知障碍的发展可能与血浆胆固醇水平升高和肥胖有关。辛伐他汀（SV）和洛伐他汀（LV）是有可能用于治疗认知缺陷的药物。本研究旨在开发并表征含有SV（SV-LNC）或LV（LV-LNC）的脂质核纳米胶囊，评估SV-LNC在认知缺陷动物模型中的作用。SV-LNC和LV-LNC制剂的平均粒径约为200nm，多分散指数低，zeta电位为负。差示扫描量热法、傅里叶变换红外光谱法、X射线衍射法和扫描电子显微镜分析表明，LNC各组分之间无反应：LV在悬浮液中结晶，SV呈分子分散状态。SV的包封率较高（98.9±1.4%），而LV的包封率较低（21.5±1.5%）。基于这些结果，SV-LNC被用于临床前研究。喂食高脂饮食（HD）的动物出现肥胖、高胆固醇血症和认知障碍, 对一些接受高脂饮食的动物进行组织学分析显示的脑部病变证实了这一点。我们观察到，游离辛伐他汀（CS3）能够降低丙酮酸激酶的酶活性，丙酮酸激酶是维持脑能量稳态的一种重要酶，但不影响接受标准饮食动物的记忆力。然而，它未能改善由高胆固醇和饱和脂肪饮食引起的认知损伤。另一方面，当辛伐他汀被“伪装”在脂质核纳米胶囊中（HNS3）时，这种认知障碍得到改善。因此，SV-LNC是治疗认知障碍的一种有前景的替代疗法。
