Self‐Exploding Beads Releasing Microcarriers

Abstract

Although significant progress in the vaccine delivery has been made during the last decades, there remain many major challenges for optimal delivery of vaccines. Two unmet needs are (i) the administration of prime and booster doses (required to generate sufficient immunity) by a single injection and (ii) the co-delivery of the adjuvant and the antigen to antigen presenting cells (APC) to enhance or bias the immune response. Enhanced antigen presentation and better immune responses have been reported in case the antigen is encapsulated in microparticles which are phagocytosed by dendritic cells. By encapsulating antigen in microparticles they are due to their sizemore targeted toAPC’s, leading to an increased antigen uptake and a 100to 1000-fold increase in antigen presentation by both MHCI and MHCII class molecules. It would thus be an enormous benefit if scientists could develop an injection that after a single shot delivers (a) multiple doses (thus avoiding the multiple injections which are currently needed) of (b) antigen and adjuvant containing microparticles to APC’s. Previously we introduced self-exploding microcapsules, 5–15mm in size, which consisted of a degradable hydrophilic microgel core surrounded by a semi-permeable polyelectrolyte membrane. Upon dispersing such microcapsules in an aqueous environment water entered the microcapsules and hydrolyzed the crosslinks of the microgel. This resulted in the swelling of the microgel core which at a certain moment ruptured the polyelectrolyte membrane thereby suddenly releasing FITC-dextran which was encapsulated in the microgel core. As schematically illustrated in Figure 1A, in this Communication we design self-exploding polyelectrolyte coated gel beads releasing micrometer-sized capsules at the time of explosion. The gel beads have a mean diameter of 150mm and are loaded with 3mm sized layer-by-layer (LbL) microcapsules. The LbL microcapsules are fabricated by sequential adsorption of (bio)polyanions and (bio)polycations