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一种新型药物传递系统:将柚皮素包封于金属-有机骨架中制成脂质体。

A Novel Drug Delivery System: the Encapsulation of Naringenin in Metal-Organic Frameworks into Liposomes.

机构信息

College of Pharmacy, Anhui Xinhua University, No.555, Wangjiang West Road, Hefei, 230088, People's Republic of China.

College of Energy, Materials and Engineering, Hefei University, Hefei, 230601, China.

出版信息

AAPS PharmSciTech. 2021 Feb 1;22(2):61. doi: 10.1208/s12249-021-01927-w.

Abstract

Poorly water-soluble naringenin (NAR) was selected as a model drug and loaded into the porous MOFs for the construction of NAR@ZIF-8 inclusion complex. By film dispersion method, NAR@ZIF-8 was further encapsulated into liposomes to fabricate a novel drug delivery system. Liposomes and a novel drug delivery system were established. Subsequently, the lipid-drug ratio, phospholipid-cholesterol ratio, and hydration temperature were investigated using the Box-Behnken design based the single factor experiment. The prepared liposomes system showed spherical or quasi-spherical shape, uniform particle size distribution, and complete structure. More specifically, the average particle size was 113.2 ± 1.4 nm, and zeta potential was - 7.536 ± 0.264 mV. Moreover, the drug release behaviors of NAR, NAR@ZIF-8, and NAR@ZIF-8 liposomes were explored in vitro. Compared with free NAR and NAR@ZIF-8 which exhibited a burst drug release, NAR@ZIF-8 liposomes showed a more sustained release behavior with 79.86% drug release in 72 h. In vitro cytotoxicity experiments showed that, compared with free NAR and NAR@ZIF-8, NAR@ZIF-8 liposomes exhibited higher inhibition efficiency on lung adenocarcinoma A549 cells and gastric cancer SGC-7901 cells in a concentration-dependent manner.

摘要

选择难溶性柚皮素(NAR)作为模型药物,负载到多孔 MOFs 中构建 NAR@ZIF-8 包合物。通过薄膜分散法,将 NAR@ZIF-8 进一步包封到脂质体中,构建新型药物传递系统。建立了脂质体和新型药物传递系统。随后,在单因素实验的基础上,采用 Box-Behnken 设计考察了载药量、磷脂胆固醇比和水化温度。所制备的脂质体系统呈球形或类球形,粒径分布均匀,结构完整。具体而言,平均粒径为 113.2±1.4nm,zeta 电位为-7.536±0.264mV。此外,还研究了 NAR、NAR@ZIF-8 和 NAR@ZIF-8 脂质体的体外药物释放行为。与表现出突释药物释放的游离 NAR 和 NAR@ZIF-8 相比,NAR@ZIF-8 脂质体表现出更持续的释放行为,72h 内释放 79.86%的药物。体外细胞毒性实验表明,与游离 NAR 和 NAR@ZIF-8 相比,NAR@ZIF-8 脂质体对肺腺癌细胞 A549 和胃癌 SGC-7901 细胞的抑制效率呈浓度依赖性。

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