Piazzini Vieri, Landucci Elisa, Graverini Giulia, Pellegrini-Giampietro Domenico E, Bilia Anna Rita, Bergonzi Maria Camilla
Department of Chemistry, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Pharmaceutics. 2018 Aug 13;10(3):128. doi: 10.3390/pharmaceutics10030128.
(1) Background: Andrographolide (AG) is a natural compound effective for the treatment of inflammation-mediated neurodegenerative disorders. The aim of this investigation was the preparation of liposomes to enhance the penetration into the brain of AG, by modifying the surface of the liposomes by adding Tween 80 (LPs-AG) alone or in combination with Didecyldimethylammonium bromide (DDAB) (CLPs-AG). (2) Methods: LPs-AG and CLPs-AG were physically and chemically characterized. The ability of liposomes to increase the permeability of AG was evaluated by artificial membranes (PAMPA) and hCMEC/D3 cells. (3) Results: Based on obtained results in terms of size, homogeneity, ζ-potential and EE%. both liposomes are suitable for parenteral administration. The systems showed excellent stability during a month of storage as suspensions or freeze-dried products. Glucose resulted the best cryoprotectant agent. PAMPA and hCMEC/D3 transport studies revealed that LPs-AG and CLPs-AG increased the permeability of AG, about an order of magnitude, compared to free AG without alterations in cell viability. The caveolae-mediated endocytosis resulted the main mechanism of up-take for both formulations. The presence of positive charge increased the cellular internalization of nanoparticles. (4) Conclusions: This study shows that developed liposomes might be ideal candidates for brain delivery of AG.
(1) 背景：穿心莲内酯（AG）是一种对治疗炎症介导的神经退行性疾病有效的天然化合物。本研究的目的是通过单独添加吐温80（LPs - AG）或与二癸基二甲基溴化铵（DDAB）联合使用（CLPs - AG）对脂质体表面进行修饰，制备能够增强AG脑部渗透能力的脂质体。(2) 方法：对LPs - AG和CLPs - AG进行物理和化学表征。通过人工膜（PAMPA）和hCMEC/D3细胞评估脂质体增加AG通透性的能力。(3) 结果：基于在粒径、均匀性、ζ电位和包封率方面获得的结果，两种脂质体均适用于肠胃外给药。该体系作为悬浮液或冻干产品在储存一个月期间显示出优异的稳定性。葡萄糖是最佳的冷冻保护剂。PAMPA和hCMEC/D3转运研究表明，与游离AG相比，LPs - AG和CLPs - AG使AG的通透性提高了约一个数量级，且细胞活力无变化。小窝介导的内吞作用是两种制剂的主要摄取机制。正电荷的存在增加了纳米颗粒的细胞内化。(4) 结论：本研究表明，所制备的脂质体可能是AG脑部给药的理想候选者。
