目的:阿昔洛韦(ACY)用于治疗口服病毒性疱疹,但溶解度和生物利用度较低。硬脂酸(SA)是亲脂性的,可以与药物结合。因此,这项研究旨在表征SA纳米颗粒在增加口腔上皮细胞对ACY的细胞摄取方面的特性。假设是SA纳米颗粒增加ACY持续释放,是稳定的,增加药物摄取。
方法:优化生产参数(超声处理的持续时间和幅度)以生产含SA的ACY的固体脂质纳米颗粒(SLN)。在不同储存条件(4°C和37°C持续1、15和45天)下表征颗粒稳定性。SLN进一步表征了它们的药代动力学特征,细胞毒性,体外通透性,以及调节基因表达和促进口腔上皮细胞吸收ACY的能力。
结果:药代动力学研究显示ACY从SLN持续和扩散释放,与15分钟的初始爆发释放。储存45d后,在4°C和37°C下保持的SLN在120分钟时显示>90%的药物的最大释放。用SLN处理的细胞表现出明显高于ACY处理的细胞内药物含量,并且显着增加了TJP-1,OCLN的遗传表达,和ECAD。
结论:该假设被接受,因为含有ACY的SA纳米颗粒可以维持药物递送并增强其在上皮细胞中的吸收。因此,SA纳米颗粒有望在治疗由HSV-1引起的口腔疱疹和其他感染中改善ACY摄取。
OBJECTIVE: Acyclovir (ACY) is used to treat oral viral herpes but has low solubility and bioavailability. Stearic acid (SA) is lipophilic and can be combined with drugs. Therefore, this study aimed to characterize the properties of SA nanoparticles in increasing the cellular uptake of ACY by oral epithelial cells. The hypothesis was that SA nanoparticles increase sustained ACY release, are stable, and increase drug uptake.
METHODS: The production parameters (duration and amplitude of sonication) were optimized to produce solid lipid nanoparticles (SLN) of SA-containing ACY. Particle stability was characterized under different storage conditions (4 °C and 37 °C for 1, 15, and 45 days). SLN were further characterized for their pharmacokinetic profile, cytotoxicity, in vitro permeability, and ability to modulate gene expression and promote ACY uptake by oral epithelial cells.
RESULTS: Pharmacokinetic studies revealed sustained and diffusional release of ACY from the SLN, with an initial burst release of 15 min. After 45 d of storage, SLN kept at both 4 °C and 37 °C showed a maximum release of > 90 % of the drug at 120 min. Cells treated with SLN presented a significantly higher intracellular drug content than those treated with ACY and significantly increased the genetic expression of TJP-1, OCLN, and ECAD.
CONCLUSIONS: The hypothesis was accepted as SA nanoparticles containing ACY can sustain drug delivery and enhance its absorption into epithelial cells. Therefore, SA nanoparticles are promising for improving ACY uptake in treating oral herpes and other infections caused by HSV-1.