Tacrolimus/hydroxypropyl-β-cyclodextrin-loaded nanoemulsions stabilized by Zein-Soluplus® nanoparticles for retinal diseases

生物利用度 化学 环糊精 溶解度 视网膜 眼药水 纳米颗粒 色谱法 水溶液 生物物理学 核化学 药理学 材料科学 生物化学 有机化学 纳米技术 生物
作者
Hay Man Saung Hnin Soe,Phyo Darli Maw,Rathapon Asasutjarit,Þorsteinn Loftsson,Phatsawee Jansook
出处
期刊:Journal of Drug Delivery Science and Technology [Elsevier]
卷期号:88: 104936-104936 被引量:2
标识
DOI:10.1016/j.jddst.2023.104936
摘要

Tacrolimus (TAC) is a medication that downregulates vascular endothelial growth factor (VEGF), an angiogenic biomarker in age-related macular degeneration. However, its poor aqueous solubility limits its ocular bioavailability. In this study, we sought to increase the aqueous solubility of TAC by complexation with hydroxypropyl-β-cyclodextrin (HPβCD). Moreover, we aimed to develop novel eye drop formulations by loading TAC into Zein nanoparticles (ZnNP), or nanoemulsions (NE) stabilized by ZnNP, with and without HPβCD. All four TAC formulations exhibited excellent physicochemical characteristics and were physically stable for at least 2 h in simulated tear fluid. However, among the formulations, TAC/HPβCD-loaded NE stabilized by Zn NP (TAC/CD-NE) showed the highest entrapment efficiency and mucoadhesive properties. It was also non-toxic to Statens Seruminstitut rabbit corneal (SIRC) and retinal pigment epithelial (ARPE-19) cells. Moreover, TAC/CD-NE was more efficiently taken up by the ARPE-19 cells compared to TAC suspended in phosphate-buffered saline and exhibited enhanced anti-VEGF activity, as evidenced by decreased VEGF mRNA and protein levels. TAC/CD-NE remained physically and chemically stable for up to three months under refrigerated conditions. Collectively, our findings suggest that TAC/CD-loaded NE stabilized by ZnNP safely and effectively delivers TAC and represents a promising eye drop formulation for retinal disease treatment.
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