Droplet-coacervated cellulose nanocrystals/chitosan microcapsules for pH-responsive oral delivery of curcumin: Role of adsorption and entrapment mechanisms.

Abstract

This study presents a sustainable strategy for developing a pH-responsive oral delivery system for curcumin by utilizing coir pith as a renewable source of cellulose nanocrystals (CNC). The CNC were combined with chitosan and ionically crosslinked with sodium tripolyphosphate via a droplet coacervation technique to form stable CNC/CS microcapsules. Curcumin loading was systematically investigated through adsorption and entrapment mechanisms, revealing distinct interaction pathways within the polymer network. The release behavior exhibited a clear formulation-dependent and pH-responsive profile. Under acidic conditions (pH 1.2), free curcumin showed rapid release (60-65%), whereas entrapment systems released only 15-35% and adsorption systems remained highly stable (1-5%). In contrast, under intestinal conditions (pH 6.8-9.0), cumulative release increased significantly, exceeding 80-90% for entrapment systems, indicating effective protection in gastric conditions and enhanced release at higher pH. In vitro studies in the presence of pepsin and probiotic Bacillus spp. further confirmed enzyme- and microbiota-responsive release behavior. The CNC/CS carriers exhibited notable mucoadhesive properties, suggesting their potential to support oral delivery performance under simulated gastrointestinal conditions. The released curcumin retained its biological activity, showing antioxidant capacity (IC50 = 114.01 μg/mL) and anti-inflammatory activity (IC50 = 110.74 μg/mL) in a release-dependent manner. Additionally, the CNC/CS system significantly improved curcumin stability, maintaining high retention (>95%) over prolonged storage compared with free curcumin. Lastly, the developed CNC/CS microcapsules demonstrate strong potential as sustainable and promising carriers for potential oral delivery applications of hydrophobic bioactive compounds.