Arif Khan, Sandeep Kumar, Anil Rajnath Singh, Mohit Agarwal, Arun Kailasiya, Junaid Qureshi
Using mesalazine as a representative drug, this review reframes colonic delivery in ulcerative colitis as an interface-dominated problem. Polymer-stabilised nano-co-crystals offer a trigger-independent strategy in which drug performance is regulated through crystal and polymer interfaces rather than fluctuating luminal conditions, providing a rational basis for further development of disease-adaptive colonic delivery systems.
BACKGROUND: Ulcerative colitis profoundly alters the colonic environment, challenging conventional oral drug delivery. Fluctuating luminal pH, irregular transit, mucus remodelling, oxidative stress and microbiota dysbiosis can destabilise trigger-dependent mesalazine formulations and contribute to inconsistent colonic drug exposure.
OBJECTIVE: This review examines the mechanistic limitations of trigger-dependent mesalazine delivery and evaluates whether increasing formulation complexity through multi-responsive systems provides sufficient benefit under the heterogeneous and unstable conditions of active ulcerative colitis.
METHODS: The review analyses how pathological changes in the colonic environment influence pH-, enzyme- and inflammation-responsive systems and considers polymer-stabilised nano-co-crystal interfacial engineering as a trigger-independent approach. Particular attention is given to crystal engineering and polymer-mediated regulation at the solid-liquid and drug-mucus interfaces.
RESULTS: Trigger-dependent systems rely on pathological cues that vary spatially and temporally during active disease, which can produce variable drug release and colonic exposure. Polymer stabilisation of nano-co-crystals provides an alternative means of controlling drug performance at the formulation interface. Polymer adsorption onto high-energy nano-co-crystal surfaces can stabilise crystalline domains, moderate dissolution, suppress aggregation and recrystallisation, and maintain controlled supersaturation under changing colonic conditions. Polymer functionality may also improve interaction with inflammation-modified mucus, prolong mucosal residence and reduce luminal washout.
CONCLUSION: Using mesalazine as a representative drug, this review reframes colonic delivery in ulcerative colitis as an interface-dominated problem. Polymer-stabilised nano-co-crystals offer a trigger-independent strategy in which drug performance is regulated through crystal and polymer interfaces rather than fluctuating luminal conditions, providing a rational basis for further development of disease-adaptive colonic delivery systems.