Asprea Martina, Tatini Francesca, Piazzini Vieri, Rossi Francesca, Bergonzi Maria Camilla, Bilia Anna Rita
Department of Chemistry, University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Institute of Applied Physics "N. Carrara" (IFAC-CNR), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy.
Pharmaceutics. 2019 Jan 16;11(1):34. doi: 10.3390/pharmaceutics11010034.
(1) Background: Andrographolide (AN), the main diterpenoid constituent of , has a wide spectrum of biological activities. The aim of this study was the development of nanocochleates (NCs) loaded with AN and based on phosphatidylserine (PS) or phosphatidylcholine (PC), cholesterol and calcium ions in order to overcome AN low water solubility, its instability under alkaline conditions and its rapid metabolism in the intestine. (2) Methods: The AN-loaded NCs (AN⁻NCs) were physically and chemically characterised. The in vitro gastrointestinal stability and biocompatibility of AN⁻NCs in J77A.1 macrophage and 3T3 fibroblasts cell lines were also investigated. Finally, the uptake of nanocarriers in macrophage cells was studied. (3) Results: AN⁻NCs obtained from PC nanoliposomes were suitable nanocarriers in terms of size and homogeneity. They had an extraordinary stability after lyophilisation without the use of lyoprotectants and after storage at room temperature. The encapsulation efficiency was 71%, while approximately 95% of AN was released in PBS after 24 h, with kinetics according to the Hixson⁻Crowell model. The in vitro gastrointestinal stability and safety of NCs, both in macrophages and 3T3 fibroblasts, were also assessed. Additionally, NCs had extraordinary uptake properties in macrophages. (4) Conclusions: NCs developed in this study could be suitable for both AN oral and parental administration, amplifying its therapeutic value.
(1) 背景：穿心莲内酯（AN）是穿心莲的主要二萜类成分，具有广泛的生物活性。本研究的目的是开发基于磷脂酰丝氨酸（PS）或磷脂酰胆碱（PC）、胆固醇和钙离子负载AN的纳米耳蜗（NCs），以克服AN的低水溶性、在碱性条件下的不稳定性及其在肠道中的快速代谢。(2) 方法：对负载AN的NCs（AN⁻NCs）进行物理和化学表征。还研究了AN⁻NCs在J77A.1巨噬细胞和3T3成纤维细胞系中的体外胃肠道稳定性和生物相容性。最后，研究了纳米载体在巨噬细胞中的摄取情况。(3) 结果：从PC纳米脂质体制备的AN⁻NCs在尺寸和均一性方面是合适的纳米载体。在不使用冻干保护剂的情况下冻干后以及在室温下储存后，它们具有非凡的稳定性。包封率为71%，而约95%的AN在24小时后在PBS中释放，动力学符合Hixson⁻Crowell模型。还评估了NCs在巨噬细胞和3T3成纤维细胞中的体外胃肠道稳定性和安全性。此外，NCs在巨噬细胞中具有非凡的摄取特性。(4) 结论：本研究开发的NCs可能适用于AN的口服和肠胃外给药，放大其治疗价值。
