Vanti Giulia, Capizzi Michela, Di Cesare Mannelli Lorenzo, Lucarini Elena, Bergonzi Maria Camilla, Ghelardini Carla, Bilia Anna Rita
Department of Chemistry, University of Florence, Via Ugo Schiff 6, 50019 Florence, Italy.
Pharmacology and Toxicology Section, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
Pharmaceutics. 2022 Feb 24;14(3):493. doi: 10.3390/pharmaceutics14030493.
Andrographolide (AG) is a natural diterpene lactone endowed with considerable therapeutic potential for treating numerous diseases, including neurological disorders, but its low aqueous solubility and scarce bioavailability limit its clinical use. To overcome this problem, AG was encapsulated in escinosomes, special nanovesicles made of escin (ESN), a natural saponin, and phosphatidylcholine. Escinosomes loaded with AG had an average size of 164.7 ± 13.30 nm, optimal polydispersity index (0.190 ± 0.0890) and high ζ-potential (-35.4 ± 0.451 mV), and significantly loaded the active substance-the encapsulation efficiency of AG was about 88%. Escinosomes allowed the prolonged release of AG over time, without burst effects-about 85% AG was released after 24 h. Morphological analysis by cryo-transmission electron microscopy showed nanovesicles with a spherical shape, unilamellar and oligolamellar structures, and dimensions in agreement with those measured by dynamic light scattering. In addition, stability studies were performed on AG-loaded escinosomes stored for one month at 4 °C. The pain-relieving efficacy of these nanovesicles was tested in a rat model of oxaliplatin-induced neuropathy. AG-loaded escinosomes, subcutaneously administered, effectively reduced the thermal allodynia characteristic of chemotherapy-induced neuropathy, enhancing and prolonging the effect of the natural compound. Overall, AG-loaded escinosomes were found to be excellent for loading AG, physically and chemically stable for one-month storage, and with controlled-release properties, making the formulation an ideal pharmacological approach for persistent pain treatment.
穿心莲内酯（AG）是一种天然二萜内酯，在治疗包括神经疾病在内的多种疾病方面具有巨大的治疗潜力，但其低水溶性和稀缺的生物利用度限制了其临床应用。为克服这一问题，AG被包裹于七叶皂苷脂质体中，七叶皂苷脂质体是由天然皂苷七叶皂苷（ESN）和磷脂酰胆碱制成的特殊纳米囊泡。负载AG的七叶皂苷脂质体平均粒径为164.7±13.30nm，具有最佳的多分散指数（0.190±0.0890）和高ζ电位（-35.4±0.451mV），且能有效负载活性物质——AG的包封率约为88%。七叶皂苷脂质体可使AG随时间延长而持续释放，无突释效应——24小时后约85%的AG被释放。冷冻透射电子显微镜的形态学分析显示纳米囊泡呈球形，具有单层和多层结构，其尺寸与动态光散射测量结果一致。此外，对在4℃下储存一个月的负载AG的七叶皂苷脂质体进行了稳定性研究。在奥沙利铂诱导的神经病变大鼠模型中测试了这些纳米囊泡的止痛效果。皮下给药的负载AG的七叶皂苷脂质体有效减轻了化疗诱导的神经病变所特有的热痛觉过敏，增强并延长了天然化合物的效果。总体而言，发现负载AG的七叶皂苷脂质体在负载AG方面表现出色，在物理和化学上可稳定储存一个月，且具有控释特性，使该制剂成为治疗持续性疼痛的理想药理学方法。
