Liu Weiqi, Guo Zhimei, Zhang Yong, Guo Yufei, Wang Ting, Liu Dahuan, Hu Chunhui
College of Pharmacy, Qinghai University, Xining 810001, China.
College of Clinical Medical, Qinghai University, Xining 810001, China.
Pharmaceuticals (Basel). 2025 May 29;18(6):819. doi: 10.3390/ph18060819.
This study aims to develop a metal-organic framework (ABZ-MOFs)-based oral drug delivery system for albendazole (ABZ) to enhance its dissolution rate and oral bioavailability. ABZ@MOF-802, ABZ@UiO-66-NH, and ABZ@MIL-125-NH were synthesized using a solvothermal method, and their physicochemical properties were characterized. The in vitro drug release was investigated under pH- and enzyme-responsive conditions, followed by transmembrane transport studies in Caco-2 cells. Finally, the oral bioavailability of ABZ@MOFs was evaluated in rats. The particle sizes of ABZ@MOF-802, ABZ@UiO-66-NH, and ABZ@MIL-125-NH were (1062.6 ± 94.8), (228.3 ± 12.3), and (502.3 ± 16.2) nm, with drug loading efficiencies of (1.71 ± 0.08%), (12.13 ± 0.04%), and (26.17 ± 0.10%), respectively. The ABZ@MOFs demonstrated structural stability in acidic environments and released ABZ under weakly acidic and neutral conditions, exhibiting distinct release profiles in the presence of different enzymes. Cellular experiments confirmed that ABZ@MOFs significantly improved transmembrane drug absorption. Pharmacokinetic analysis revealed that the bioavailability of ABZ@UiO-66-NH and ABZ@MIL-125-NH was 10.3-fold and 1.8-fold higher, respectively, compared to ABZ. The ABZ@MOFs systems effectively improved ABZ dissolution and oral bioavailability, with ABZ@UiO-66-NH showing a dual response mechanism to pH and enzymes.
本研究旨在开发一种基于金属有机框架(ABZ - MOFs)的阿苯达唑(ABZ)口服给药系统,以提高其溶解速率和口服生物利用度。采用溶剂热法合成了ABZ@MOF - 802、ABZ@UiO - 66 - NH和ABZ@MIL - 125 - NH,并对其理化性质进行了表征。在pH和酶响应条件下研究了体外药物释放,随后在Caco - 2细胞中进行了跨膜转运研究。最后,在大鼠中评估了ABZ@MOFs的口服生物利用度。ABZ@MOF - 802、ABZ@UiO - 66 - NH和ABZ@MIL - 125 - NH的粒径分别为(1062.6±94.8)、(228.3±12.3)和(502.3±16.2)nm,载药效率分别为(1.71±0.08)%、(12.13±0.04)%和(26.17±0.10)%。ABZ@MOFs在酸性环境中表现出结构稳定性,在弱酸性和中性条件下释放ABZ,在不同酶存在下呈现出不同的释放曲线。细胞实验证实ABZ@MOFs显著提高了跨膜药物吸收。药代动力学分析表明,与ABZ相比,ABZ@UiO - 66 - NH和ABZ@MIL - 125 - NH的生物利用度分别提高了10.3倍和1.8倍。ABZ@MOFs系统有效提高了ABZ的溶解率和口服生物利用度,其中ABZ@UiO - 66 - NH对pH和酶表现出双重响应机制。