Although significant progress in the vaccine delivery has been made during the last decades, there remain many major challenges for optimal delivery of vaccines. [1,2] 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. [3][4][5][6] By encapsulating antigen in microparticles they are due to their size more targeted to APC's, leading to an increased antigen uptake and a 100-to 1000-fold increase in antigen presentation by both MHC I and MHC II 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, 5-15 mm in size, which consisted of a degradable hydrophilic microgel core surrounded by a semi-permeable polyelectrolyte membrane. [7][8][9][10] 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 150 mm and are loaded with 3 mm sized layer-by-layer (LbL) microcapsules. The LbL microcapsules [11][12][13][14][15] are fabricated by sequential adsorption of (bio)polyanions and (bio)polycations (named LbL [16] coating) onto a spherical template followed by the decomposition of this template. We show that when the polyelectrolyte coated gel beads explode the smaller LbL microcapsules become suddenly released. We and others have reported before that LbL microcapsules (1) can encapsulate high amounts of proteins in an intact state, [17][18][19][20] and (2) are taken up and degraded by dendritic cells, both in vitro as well as in vivo. [21,22] In view of this, we reasoned that self-exploding gel beads releasing antigen containing LbL microcapsules at different times after injection could become promising materials for vaccination purposes. The specific aim of this paper is two-fold. First, we aim to show that a polyelectrolyte coated spherical gel bead can be loaded with LbL microcapsules.Next we aim to demonstrate the sudden release of these LbL microcapsules upon the rupturing of the polyelectrolyte shell on the surface of the gel beads. Calcium carbonate (CaCO 3 ) core ...

Abstract. The potential of poly(ethylene oxide)-poly(propylene oxide) block copolymers Pluronic® F127 (PF127) and Tetronic® 304 (T304), 904 (T904) and 1307 (T1307) as components of solid self-(micro) emulsifying dosage forms, S(M)EDDS, was evaluated. The dependence of the self-associative properties of Tetronics on pH explained the low ability of the micelles to solubilize griseofulvin at acid pH (sevenfold increase) compared to at alkaline pH (12-fold). Blends of polyglycolyzed glycerides (Labrasol, Labrafac CC, and Labrafil M 1944CS) with each copolymer at two different weight ratios (80:20 and 60:40) were prepared, diluted in water, and characterized in terms of globule size, appearance and griseofulvin solubility. The blends with Labrasol led to microemulsions that are able to increase drug solubility up to 30-fold. SMEDD hard gelatine capsules filled with griseofulvin and Labrasol or Labrasol/ copolymer 80:20 showed a remarkable increase in drug solubility and dissolution rate, particularly when T904, T1307 or PF127 was present in the blend. This effect was more remarkable when the volume of the dissolution medium was 200 ml (compared to 900 ml), which can be related to a higher stability of the microemulsion when there is a greater concentration of the copolymer and glyceride in the medium.