pH-activated liquid microdroplet carrier for enhanced phycocyanin oral delivery and sustained bioactivity post-digestion

Although C-phycocyanin (PC) possesses various therapeutic functions, it is highly unstable under gastrointestinal (GI) conditions involving digestive enzymes and pH variations, leading to rapid degradation and subsequent loss of bioactivity before absorption. A protective oral delivery system is therefore essential to enhance its bioavailability and delivery efficiency. In this study, a water-immiscible, pH-responsive microdroplet system was developed using fish gelatin (FG) and fucoidan (FC) as carriers to protect and deliver PC to the small intestine. Stable complex coacervation between FG and FC at pH 3.3 and a mixing weight ratio of 80:20 formed liquid microdroplets, whereas the combination of bovine gelatin type B (GB) and FC yielded solid precipitates. Under these optimized conditions, PC was successfully encapsulated with high efficiencies (> 98 %). During sequential simulated digestion, COA exhibited pH-triggered dissociation and enzymatic degradation, enabling sustained PC retention in gastric fluid and selective release in the intestinal environment (pH 7).Importantly, PC released from COA preserved its structural stability during simulated digestion and demonstrated superior bioactivities, confirmed by nitric oxide generation in macrophages and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assays, compared to unprotected PC. Taken together, this study establishes marine-derived coacervates as pH-activated, sustainable carriers that ensure protection of delicate bioactive proteins and targeted intestinal delivery.