Microfluidic nano-in-microcapsules for ph-responsive colonic delivery of 5-ASA: A moving-boundary kinetic approach.

Abstract

The performance of targeted oral delivery systems for hydrophobic drugs like 5-aminosalicylic acid is limited by variable release kinetics and premature release in the upper gastrointestinal tract. To address this challenge, monodisperse 5-aminosalicylic acid nanocrystal-in-hydroxypropyl methylcellulose acetate succinate (5-ASA NCs@HPMCAS) composite microcapsules were prepared via microfluidic interfacial assembly and antisolvent precipitation. Droplet-templated solidification yielded microcapsules with an average diameter of 28.33 μm, a coefficient of variation < 3%, a drug loading of 20.4 wt% and an encapsulation efficiency of 83.3%. Driven by the pH-dependent transition of the HPMCAS shell, the microcapsules remained structurally intact under simulated gastric and proximal intestinal conditions (pH < 6.0) but underwent rapid interfacial erosion around pH 6.1. The model payload was released within approximately 3 min at pH 7.2 under quiescent in vitro conditions, while 5-ASA release reached 88.5% at pH 6.5 over 4 h. Ex vivo GI imaging of DiR-labeled microcapsules provided preliminary evidence of upper-GI retention and lower-GI localization after oral administration. Residual ethyl acetate was approximately 217 ppm, while dimethyl sulfoxide was below the assay's quantification range. A 24-hour Caco-2 assay showed cell viability above 90%, supporting preliminary in vitro cytocompatibility under the tested conditions. The uniform particle size also enabled comparison between single-particle moving-boundary kinetics and macroscopic release behavior, providing a physicochemical basis for pH-responsive oral delivery.