Chitosan-based metal-organic frameworks for improving the oral delivery and antibacterial activity of natural...

In current research on the antibacterial applications of natural flavonoid compounds, three major limitations-poor solubility, low bioavailability, and limited permeability-have restricted their therapeutic potential and have emerged as key barriers to clinical translation. This study sought to overcome these challenges by developing a novel plant-based drug delivery system. A β-cyclodextrin-based metal-organic framework (CD-MOF) was synthesized via a low-energy ultrasound-assisted thermal solvent method. The framework was then coated with carboxymethyl chitosan and chitosan oligosaccharides with genipin and used to coencapsulate quercetin, luteolin, kaempferol, and apigenin. Among the formulations, the carboxymethyl chitosan-modified CD-MOF (CMCS@CD-MOF) exhibited the highest encapsulation efficiency for quercetin. Drug adsorption studies demonstrated that the system followed pseudo-first-order kinetics and the Langmuir model, with an average loading capacity of 22.78 % for quercetin. In vitro release tests revealed greater release under intestinal conditions, following a sustained-release profile driven by Fick diffusion. Toxicity testing revealed that the flavonoid carriers were safe across the tested concentrations. The quercetin-loaded delivery system also showed strong antibacterial effects, particularly against gram-negative bacteria, with minimum inhibitory concentrations (MBCs = 40.96 μg/mL). The pharmacokinetic results revealed a threefold increase in bioavailability and a significantly extended circulation time compared with those of free quercetin. These findings support the potential of naturally derived materials for improving the delivery and therapeutic performance of plant-based bioactive compounds, offering a sustainable and safe approach for future medical applications.