Oral supramolecular nanovectors for dual natural medicine codelivery to prevent gastric mucosal lesion†
The oral administration of a single formulation loaded with more than one natural medicine to treat chronic diseases has advantages such as convenience, effectiveness, and economy. Here, using biomaterials approved by the drug administration, we fabricated supramolecular nanovectors containing dual natural medicines to prevent gastric mucosal lesions. Nanovectors exhibited superior intestinal absorption and bioavailability, which might be due to their high dispersion, good muco-adhesiveness, blood-lymph circulation transport, lipid sensing, and protective effects. Molecular docking results clarified the possible mechanisms in aspects of efflux pump (p-glycoprotein and multidrug resistance protein 1) inhibition effects, metabolic enzyme (cytochrome P450 3A4/1A2) blocking effects, serum albumin deposit effects, and dual drug interaction effects. Nanovectors decreased ethanol-induced gastric mucosal lesions by lowering the gastric ulcer index, preventing oxidative damage, decreasing interleukin-6, tumor necrosis factor-α and malondialdehyde, increasing glutathione, superoxide dismutase, and prostaglandin E2 levels. The interactions of inhibitor of nuclear factor-κB or κB kinase-related proteins and dual drugs or nanovector components were simulated computationally to provide an understanding of the gastro-protective action mechanism. In all, industrializable supramolecular nanovectors could effectively co-deliver dual natural medicines via the oral route by improving the pharmacokinetic behavior and exerting protective efficacy of the gastric mucosa by decreasing the oxidative stress and inflammatory level.