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. [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 ...

Polymersomes in Polymersomes: Multiple Loading and Permeability Control

“…[7] Other reports evidenced the biomedical impact of such vesosomes for transcutaneous, [8] and oral administration, [9] important areas in drug delivery and cancer therapy. More complex or compartmentalized structures in general, have started to appear because they enable an unprecedented level of control, in particular in the fields of drug delivery [10] and confined reactors. [11] However, it is still very challenging [12] to encapsulate multiple distinct components in a single compartment [13] and control their stability and release properties.…”

Polymeric Multilayer Capsules in Drug Delivery

“…When the swelling pressure exceeds the tensile strength of the PMLC membrane, the capsule ruptures and the encapsulated species are released. [120][121][122][123][124][125][126][127] Figure 5 shows a series of confocal microscopy images of such an exploding capsule that was loaded with fluorescent latex beads as a model. Remarkably, the released latex beads are able to travel relatively large distances within a short time frame, compared to purely Brownian motion.…”

Polymeric multilayer capsules delivering biotherapeutics

“…A tightly optimized coating composition yielded so-called self-exploding capsules that retained their payload during degradation of the microgel core. [34,35] However, upon total degradation, when the osmotic pressure of the microgel core exceeds the tensile strength of the capsule membrane, the capsule explodes and released its payload in a pulsatile fashion. [36] Recently the Trau group reported on a novel so-called reverse-phase LbL encapsulation technique.…”