Abstract Background Oral delivery of biologics, peptides, and live microbiotics remains limited by degradation in the gastric environment. Conventional methacrylate-based enteric coatings are constrained by fixed pH thresholds, potential toxicity, and regulatory restrictions 1. We developed a natural, biodegradable encapsulation system—ApiVault—based on bacterial cellulose (BC) and cellulase, enabling “programmable” pH-triggered release in defined intestinal regions (Ileum, or colon) and offering an alternative to synthetic enteric coatings. The programmed release can be obtained because intestinal transit times are relatively constant and independent of feed state 2. Methods Encapsulation prototypes were fabricated using industrial-grade BC combined with a cellulase enzyme which is inhibited under gastric pH but active under intestinal pH 3. In vitro diffusion assays and percolation-based release models were used to map dissolution kinetics across varying membrane thickness, enzyme concentration, and material parameters. Release profiles were quantified under simulated gastrointestinal pH and time conditions, corresponding to physiological transit times in the stomach, small intestine, and colon 2. Results The encapsulation exhibited gastro-resistance until 6 h at pH 1.2 and predictable dissolution initiation at ∼ pH ≥ 4.0. By modulating four formulation factors, controlled release could be tuned from 1.0 h (∼ Ilium) to 6. 0 h (∼ colonic) onset (Figure 1). The high reproducibility of the degradation process demonstrated high consistency across batches. The encapsulation achieved site-specific substance release within physiological transit ranges for all intestinal compartments, confirming its capability for targeted delivery. Industrial sources of both BC and cellulase were identified, supporting scalable production. Conclusion The ApiVault system provides a fully natural, biocompatible alternative to synthetic polymers, enabling safe and tunable oral delivery of biologics and live microbiotics for IBD therapy. Its pH-responsive mechanism is activated at a lower pH then synthetic enteric coating. This is superior to synthetic coatings since intestinal pH 6.0 sometimes has been recorded in IBD patients. Its adjustable kinetics support site-specific release in the distal intestine or colon, offering a promising platform for next-generation oral formulations targeting mucosal inflammation in Crohn’s disease and ulcerative colitis. References: 1. Czarnocka JK, Alhnan MA. Gastro-resistant characteristics of GRAS-grade enteric coatings for pharmaceutical and nutraceutical products. Int J Pharm. 2015;486(1-2):167-174. doi: 10.1016/j.ijpharm.2015.03.039 2. Abuhelwa AY, Foster DJR, Upton RN. A quantitative review and meta-models of the variability and factors affecting oral drug absorption. Part II: gastrointestinal transit time. AAPS J. 2016;18(5):1322-1333. doi:10.1208/s12248-016-9953-7. PMID: 27439620.3. 3. Apillet ApS. NOVEL ORAL COMPOSITION. WO2020035475A/EP3836905. Published 2020. Conflict of interest: Dr. Christensen, Anders: I am founder and CEO of Apillet ApS, developing cellulose-based oral biologic delivery systems I am an employee and shareholder of Apillet ApS. I hold a patent related to oral biologic delivery (WO2020035475A1). I hold shares in Novo Nordisk Lunde Petersen, Carsten: I am cofounder of Apillet ApS, developing cellulose-based oral biologic delivery systems I am an employee and shareholder of Apillet ApS. I hold a patent related to oral biologic delivery (WO2020035475A1). I hold shares in: Novo Nordisk Lundbeck Zealand Pharma Eli Lili Genmab Pfizer Bavarian
Christensen et al. (Thu,) studied this question.