Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore, Karnataka, India.
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
F1000Res. 2022 Dec 19;11:1535. doi: 10.12688/f1000research.128874.1. eCollection 2022.
Asiatic acid (AA) is a naturally occurring triterpenoid derivative of (CA) with neuroprotective effect. The study aimed to design an ideal oral drug delivery system to treat Alzheimer's disease (AD) and develop chitosan-embedded liposomes comprising an extract of CA (CLCAE) and compare them with the chitosan-coated liposomes of asiatic acid (CLAA) for oral delivery to treat the initial phases of AD. The solvent evaporation technique was used to develop CLCAE and CLAA, optimised with the experiment's design, and was further evaluated. Nuclear magnetic resonance (NMR) studies confirmed coating with chitosan. (TEM) and atomic force microscopy (AFM) indicated the successful formation of CLCAE and CLAA. Differential scanning colorimetry (DSC) confirmed the drug-phospholipid complex. Furthermore, the rate of release of CLCAE and CLAA was found to be 69.43±0.3 % and 85.3±0.3 %, respectively, in 24 h. permeation of CLCAE and CLAA was found to be 48±0.3 % and 78±0.3 %, respectively. In the Alcl3-induced AD model in rats, disease progression was confirmed by Y-maze, the preliminary histopathology evaluation showed significantly higher efficacy of the prepared liposomes (CLCAE and CLAA) compared to the extract (CAE) and they were found to have equivalent efficacy to the standard drug (rivastigmine tartrate). The considerable increase in pharmacodynamic parameters in terms of neuronal count in the CLAA group indicated the protective role against Alcl3 toxicity and was also confirmed by assessing acetylcholine (Ach) levels. The pharmacokinetic study, such as C , T , and area under curve (AUC) parameters, proved an increase in AA bioavailability in the form of CLAA compared to the pure AA and CLCAE forms. The preclinical study suggested that CLAA was found to have better stability and an ideal oral drug delivery system to treat AD.
亚洲酸（AA）是一种天然存在的三萜类衍生物，具有神经保护作用。本研究旨在设计一种理想的口服药物传递系统来治疗阿尔茨海默病（AD），并开发包含 CA 提取物的壳聚糖嵌入脂质体（CLCAE），并将其与壳聚糖包被的亚洲酸脂质体（CLAA）进行比较，用于口服治疗 AD 的早期阶段。溶剂蒸发技术用于开发 CLCAE 和 CLAA，并用实验设计进行了优化，并进一步进行了评估。核磁共振（NMR）研究证实了壳聚糖的涂层。（TEM）和原子力显微镜（AFM）表明成功形成了 CLCAE 和 CLAA。差示扫描量热法（DSC）证实了药物-磷脂复合物。此外，发现 CLCAE 和 CLAA 的释放率分别为 24 小时内 69.43±0.3%和 85.3±0.3%。CLCAE 和 CLAA 的渗透率分别为 48±0.3%和 78±0.3%。在 Alcl3 诱导的 AD 大鼠模型中，通过 Y 迷宫证实了疾病的进展，初步的组织病理学评估表明，与对照（CAE）相比，制备的脂质体（CLCAE 和 CLAA）具有更高的疗效，并且与标准药物（酒石酸赖氨丁醇）等效。CLAA 组在神经元计数方面药效学参数的显著增加表明了对 Alcl3 毒性的保护作用，并通过评估乙酰胆碱（Ach）水平得到了证实。药代动力学研究，如 C、T 和曲线下面积（AUC）参数，证明了以 CLAA 形式的 AA 生物利用度增加，与纯 AA 和 CLCAE 形式相比。临床前研究表明，CLAA 被发现具有更好的稳定性和理想的口服药物传递系统来治疗 AD。
