In Situ Biofabrication of Microbial Cellulose Capsules Carrying Cubosomes: Toward Colon Targeted Multidrug Delivery

The colon is a main absorption site (nutrients and drugs) and a target for oral therapeutic delivery. However, the latter is challenged by the fact that most drugs degrade during transit in the gastrointestinal tract (GIT). Herein, we rationally designed a universal controlled-release system based on cubosomes contained in microbial nanocellulose capsules that enabled oral administration and pH-triggered delivery of bioactives. We show that the bicontinuous cubosome structure allows the simultaneous incorporation of drugs with differing polarity or surface energy. Furthermore, the multidrug cubosomes combined with the cellulose carrier by in situ biofabrication was demonstrated as a route toward multicomponent 3D capsules with added protection in the GIT. The obtained capsules were subsequently coated with sodium alginate to enable responsiveness, achieving dual cargo-controlled release and site-specific administration. In sum, we successfully engineered pH-responsive, nontoxic microcapsules as a versatile platform for colon-targeted multidrug delivery.