Biodegradable Polyelectrolyte Microcapsules: Antigen Delivery Tools with Th17 Skewing Activity after Pulmonary Delivery

Abstract

Because of their large surface area, the lungs appear an attractive route for noninvasive vaccine delivery, harboring the potential to induce local mucosal immune responses in addition to systemic immunity. To evoke adaptive immunity, Ags require the addition of adjuvants that not only enhance the strength of the immune response but also determine the type of response elicited. In this study, we evaluate the adjuvant characteristics of polyelectrolyte microcapsules (PEMs) consisting of the biopolymers dextran-sulfate and poly-l-arginine. PEMs form an entirely new class of microcapsules that are generated by the sequential adsorption of oppositely charged polymers (polyelectrolytes) onto a sacrificial colloidal template, which is subsequently dissolved leaving a hollow microcapsule surrounded by a thin shell. Following intratracheal instillation, PEMs were not only efficiently taken up by APCs but also enhanced their activation status. Pulmonary adaptive immune responses were characterized by the induction of a strongly Th17-polarized response. When compared with a mixture of soluble Ag with empty microcapsules, Ag encapsulation significantly enhanced the strength of this local mucosal response. Given their unique property to selectively generate Th17-polarized immune responses, PEMs may become of significant interest in the development of effective vaccines against fungal and bacterial species.

Encapsulation Performance of Layer-by-Layer Microcapsules for Proteins

“…15,16 As an example, our group encapsulated antigen proteins in polyelectrolyte microcapsules consisting of dextran sulfate and poly-L-arginine; we showed that such capsules degrade in dendritic cells through proteases and subsequently release the antigen. 3,17 Besides tuning the permeability of the capsule shell by variations in shell thickness, the capsule surface can also be functionalized by e.g. poly(ethylene glycol), 18 lipids, 19 antibodies, 20 dyes 21 and nanoparticles.…”

Polymeric multilayer capsules delivering biotherapeutics

“…Despite their relatively big size, LbL capsules are readily internalized not only by professional phagocytes (DCs [25,72,73] and macrophages [74] largely reduced by cytochalasin D, indicating particle internalization involves an actin dependent process. Furthermore, particle uptake was reduced by incubation with rottlerin, suggesting macropinocytosis as the predominant route of uptake in DCs.…”

“…So far the following biotherapeutics have been encapsulated in CaCO 3 templated PMLC: dextran, a-lactalbumin, lysosyme, horseradish peroxidise, glucose oxidase, catalase, ovalbumin, bovie serum albumin, achymotrypsin, insulin DNA and pronase. [15,17,18,[24][25][26][27][28] A third category of template particles that have gathered considerable attention in literature are hydrogel beads. Hydrogels are strongly hydrated 3D networks which, due to their aqueous environment offer good preservation of the biotherapeutics' bioactivity upon encapsulation.…”

“…Importantly, the DS/pARG capsules retained their structural integrity before cellular uptake, but got rapidly degraded after internalization. [80] DS/pARG capsules were also explored as antigen delivery vehicles for pulmonary immunisation, [72] which recently has draw a lot of attention as it allows a noninvasive route of delivery and might harbour the benefit of inducing local mucosal immune responses in addition to systemic immunity. Pulmonary delivery of DS/pARG capsules induced a transient inflammatory response with recruitment of mainly monocytes and granulocytes.…”

Intracellular delivery and sensing based on polyelectrolyte multilayer capsules

“…The most widespread and best understood pair of polymers is the system of poly(styrene sulfonate) (PSS) and poly(allyamine hydrochloride) (PAH). However, there are many other polymers in use and it is also possible to produce biodegradable capsules made of polymers that can be digested/metabolized inside living cells, for example by proteases present in the lysosome [7,8]. There are two ways to load the capsules, the coprecipitation method, where the cargo is entrapped in the template and remains inside the capsules after removal of the template material, and the postloading method, where the permeability of the capsules can be controlled externally by variation of pH, salt concentration or temperature [9], and the cargo can be loaded into the empty capsules after the synthesis [10].…”