Sodium Carboxymethyl Cellulose-Stabilised Multiple Emulsions with pH-Sensitive Behaviour, Enhanced Stability and Mucoadhesion for Oral Delivery of Chemopreventive Agents

<b>Background/Objectives:</b> The oral administration of chemopreventive agents for colorectal cancer (CRC) remains limited by their low solubility, instability, and limited intestinal absorption. This study develops sodium carboxymethyl cellulose (CMC)-stabilised water-in-oil-in-water (W/O/W) multiple emulsions as pH-responsive carriers for co-delivery of resveratrol and selenium-two complementary chemopreventive compounds. <b>Methods:</b> Multiple emulsions differing in droplet size (small-droplet emulsions, SDE; large-droplet emulsions, LDE) and CMC concentration (0.0-0.5% <i>w</i>/<i>w</i>) are prepared in a Couette-Taylor Flow contactor. The study involves physicochemical characterisation of emulsions (droplet size, stability, rheological behaviour, ζ-potential, encapsulation efficiency), evaluation of release profiles under simulated gastric pH (2.0) and intestinal pH (7.0) conditions, including pathological environments (pH = 5.5), and ex vivo assessment of mucoadhesion using porcine intestinal tissue. <b>Results:</b> SDE and LDE containing CMC (0.0-0.5% <i>w</i>/<i>w</i>) exhibit a complex "drop-in-drop" structure, with Sauter mean diameters of approximately 9-12 μm and 23-25 μm, respectively, and high encapsulation efficiencies (>91%). Increasing CMC concentration enhances viscosity and induces more negative ζ-potential, confirming polymer adsorption at the oil-water interface. Under simulated gastric pH = 2.0, compound release remains limited (≤15%), whereas gradual/sustained release is observed under simulated intestinal pH (5.5/7.0). Mucoadhesion increases with polymer concentration, reaching ~90% for SDE and ~70% for LDE at 0.5% <i>w</i>/<i>w</i> CMC, and remains above 50% under simulated pathological conditions. <b>Conclusions:</b> The study demonstrates that CMC incorporation improves the structural stability, modulates the release behaviour, and enhances the mucoadhesive properties of W/O/W multiple emulsions. These findings suggest that CMC-stabilised emulsions may be further explored as oral delivery vehicles for CRC chemoprevention.