One-step prepared nano-in-micro microcapsule delivery vehicle with sequential burst–sustained drug release for the targeted treatment of inflammatory bowel disease

Abstract

Orally targeted drug delivery for treating colonic diseases has attracted much attention because this method can be used as a better alternative to conventional administration of high drug doses, which usually exposes patients to serious systemic toxicity. Here, a pH-responsive nano-in-micro composite as a drug-delivery vehicle for the targeted therapy of inflammatory bowel disease (IBD) is designed and prepared using a one-step droplet microfluidic method with a water-in-oil-in-water manner. The microcapsules, encapsulating both free drugs and drug-loaded nanoparticles (NPs), appear as bowl-shaped spheres with a non-uniform shell thickness. Under colonic pH, the thin concave lamella of the HPMCAS-based shells rapidly ruptures and releases the inner free drug to achieve burst drug release for a sufficiently high and effective concentration of the drug. Subsequently, the gradual decomposition of PLGA-based drug-loaded NPs results in sustained drug release. The sequential burst–sustained drug release is consistent with the pharmacokinetics and medication needs of IBD. In vitro inflammation inhibition experiments further reveal that the nano-in-micro microcapsules can quickly alleviate the inflammatory response at the site of inflammation by reducing the intracellular ROS level and the expression of proinflammatory cytokines. These results demonstrate the success of the targeted drug-delivery model with the function of sequential burst–sustained drug release for IBD therapy.