Preparation and Evaluation of an Oral Administration System of Albendazole-Metal-Organic Framework Based on Dual Response to pH and Enzymes

<b>Objective:</b> 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. <b>Methods:</b> ABZ@MOF-802, ABZ@UiO-66-NH₂, and ABZ@MIL-125-NH₂ 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. <b>Results:</b> The particle sizes of ABZ@MOF-802, ABZ@UiO-66-NH₂, and ABZ@MIL-125-NH₂ 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-NH₂ and ABZ@MIL-125-NH₂ was 10.3-fold and 1.8-fold higher, respectively, compared to ABZ. <b>Conclusions:</b> The ABZ@MOFs systems effectively improved ABZ dissolution and oral bioavailability, with ABZ@UiO-66-NH₂ showing a dual response mechanism to pH and enzymes.