Elastic osmotic capsules mimic bolus injection with high release at delayed burst

The need for repeated administration of vaccines is costly, logistically challenging and leads to reduced compliance. Osmosis-driven swelling and rupture has been proposed as a mechanism for delayed burst release to mimic follow-up (booster) injections without requiring further intervention. The use of microparticles does not guarantee a single bolus release, and previous studies using monolithic implants failed to demonstrate high instant release at the moment of burst. In this study we developed elastic capsules based on a caprolactone-lactide copolymer that released 75 ± 8 % of their contents instantly after up to several weeks of incubation. Capsules swelled up to 5x their original mass through highly reproducible osmosis-induced water uptake. The water uptake rates depended on osmotic strength and could be approximated with a numerical model revealing a water permeability of 3.6±0.2 mm2/(Pa∙day) for all 118 capsules. The moment of burst depended on osmotic strength and capsule stiffness (median times varied from 16 to 37 days) and showed large scatter. The capsule material was nontoxic to a macrophage cell line and degraded through bulk hydrolysis, with an extrapolated completion time of 8 months. The capsules were administered successfully in bovine cadavers with a widely used applicator.