Development of a novel polymeric osmotically triggered delayed release vaccine delivery device

Abstract

In this work, a delayed release osmotically triggered delivery device was developed that was able to release a payload after a delay of approximately 21 days in a consistent and reproducible manner. The device was constructed out of a flexible polycaprolactone photo-cured network, which expelled up to 21.5 % of its total payload after burst, enabling close to bolus-like release profile. Characterisation of the factors that control the delay of release was also performed, with evidence demonstrating that it was advantageous to adjust material permeability and device wall thickness over manipulation of the osmogent concentration, in order to maintain burst reproducibility. The photo-cured polycaprolactone network was shown to be degradable under simulated physiological conditions, and there was no evidence of cytotoxicity after 11 days of direct contact with primary dermal fibroblasts. This study provides strong evidence to support further development of flexible biomaterials with the aim of continuing improvement of the device burst characteristics in order to provide the greatest chance of the devices succeeding with in-vivo vaccine booster delivery. Additionally, a polycaprolactone-based stereolithography resin was developed that retains a degree of semi-crystallinity, thus providing significantly improved toughness while retaining biocompatibility. Benzyl alcohol was shown to be a more suitable diluent than dioxane for the formulation of PCL macromer photo-curable resins. An improved automated dip-coat-curing machine for the production of the device tubular part was also constructed.