Generation of microfluidic-based pH- and colon enzyme-responsive pectin-alginate core-shell microcarriers: tunable drug release for oral applications

Oral delivery of therapeutic agents to the colon remains challenging due to premature drug release and limited control over drug transport through the gastrointestinal tract. In this study, pH- and colon enzyme-responsive pectin–alginate core–shell microcarriers were developed using a microfluidic-based generation approach for controlled oral drug delivery. Mesalazine-loaded pectin cores were encapsulated within an alginate shell containing polydopamine nanoparticles, providing a multifunctional carrier system. Monodisperse core–shell microdroplets were generated, with an average diameter of 7.03 ± 1.33 µm. The microcarriers exhibited high encapsulation efficiency and drug loading capacity, reaching 89% and 9%, respectively. In vitro release studies under sequential gastrointestinal conditions demonstrated that the core–shell architecture inhibited drug release in simulated gastric fluid and eliminated the early burst release observed in single-layer microparticles. The release profile depended on the interplay between particle size and crosslinking density. At lower crosslinking levels, particle size predominantly governed drug diffusion, with larger microcarriers exhibiting slower release due to the longer diffusion pathways. At higher crosslinking density, the compact polymeric network became predominant, restricting drug diffusion despite the reduced particle size. The developed microcarriers reduced intracellular reactive oxygen species levels, highlighting their potential as a therapeutic platform for inflammatory bowel disease applications.