3D Bioprinting of an Oral Colon Delivery System for Precision Bacteriotherapy

Objectives: A customizable 3D-bioprinted core-in-shell platform was developed for time-dependent oral colon delivery of live microorganisms. The system conveyed Lacticaseibacillus paracasei as a model bacterial species within a monolithic core, which was surrounded by a swellable hydroxypropyl cellulose barrier, imparting a lag phase of programmable duration, and by an enteric outer layer, protecting the dosage form during unpredictable gastric residence. Methods: Pastes of different compositions were investigated to shape the core. Core and core-in-shell units were fabricated from digital models using a bioprinter equipped with a high-precision plunger dispenser and pressure-based thermoplastic printhead. The printed units were characterized in terms of mass, dimensions, mechanical properties and release performance using paracetamol as a reference tracer. Bacterial viability was evaluated during screening of the formulation components and after each processing step by manual counting of colony-forming units. Results: A mannitol-based formulation was selected for fabrication of the core, offering a favorable balance of printability, physico-technological properties, release behavior and ability to preserve bacterial viability. Two-layer core-in-shell systems were manufactured via a dual-printing operating mode. The desired in vitro performance was attained, with no release under acidic conditions, a lag phase in pH 6.8 fluid and a subsequent release profile comparable with that generated by the core as such. Viability studies demonstrated that compounding, core printing, shell deposition and drying did not adversely affect L. paracasei survival. Conclusions: 3D bioprinting was proved to be a versatile technique for the manufacturing of oral colon delivery systems containing probiotics or live biotherapeutics.