Encapsulation performance of layer-by-layer microcapsules for proteins

This study reports on the encapsulation efficiency of proteins in dextran sulfate/poly-l-arginine-based microcapsules, fabricated via layer-by-layer assembly (LbL). For this purpose, radiolabeled proteins are entrapped in CaCO3 microparticles, followed by LbL coating of the CaCO3 cores and subsequent dissolving of the CaCO3 using EDTA. To allow to improve protein encapsulation in LbL microcapsules, we studied all steps in the preparation of the microcapsules where loss of protein load might occur. The encapsulation efficiency of proteins in LbL microcapsules turns out to be strongly dependent on both the charge and molecular weight of the protein as well as on the number of polyelectrolyte bilayers the microcapsules consist of

Tailoring layer-by-layer capsules for biomedical applications

Polymeric capsules have attracted great interest as versatile carrier systems in the area of medicine and pharmaceutics. These capsules are made by stepwise layer-by-layer adsorption of polymers onto a template core, which can be removed to produce hollow capsules. The cavity of these capsules can host various cargo molecules while the capsules' wall can be functionalized towards desired properties by embedding specific moieties into the multilayers. Tuning of the capsules' properties influences their interaction with cells and tissues and paves the way towards the development of stimuli-responsive capsules releasing their payload at a target site. In this review, we describe the generation of tailored layer-by-layer capsules and focus hereby on numerous potential applications of this multifunctional delivery platform in biomedical settings. We review the current status in the field and discuss the opportunities, as well as the hurdles, to be overcome to successfully transfer this technology to therapeutic and diagnostic applications

Particulate vaccines: on the quest for optimal delivery and immune response

Subunit vaccines offer a safer alternative to traditional organism-based vaccines, but their immunogenicity is impaired. This hurdle might be overcome by the use of micro- and nanodelivery systems carrying the antigen(s). This review discusses the rationale for the use of particulate vaccines and provides an overview of antigen-delivery vehicles currently under investigation. It further highlights the cellular uptake, antigen processing and the presentation by antigen-presenting cells because these processes are partially governed by particle characteristics and eventually determine the immunological outcome. Finally, we address the attractive concept of concomitant delivery of antigens and immunopotentiators. The condensed knowledge could be an asset for rationally designing antigen-delivery vehicles to obtain safe and efficacious vaccines

Lyophilization of protein-loaded polyelectrolyte microcapsules

Purpose To evaluate if lyophilization can be used to obtain a dry formulation of polyelectrolyte microcapsules, which have emerged as a new class of microparticles for the encapsulation and delivery of biomacromolecules. Methods Microcapsules composed of dextran sulfate and poly-L-arginine were obtained by coating CaCO(3) microparticles by means of the layer-by-layer technique. Microcapsules were lyophilized using different stabilizers; intactness was checked by CLSM and SEM. Horseradish peroxidase was encapsulated as model enzyme and retained activity after freeze-drying was determined using a fluorescence assay. Ovalbumin was encapsulated as model antigen; immunogenicity after lyophilization was evaluated in vitro by a T-cell proliferation assay and in vivo by measuring the antibody titer in mice. Results The results clearly demonstrate the necessity of using polyols in the formulation to prevent rupture of the microcapsules and to preserve the activity of encapsulated enzymes. Lyophilized microcapsules appeared as a promising adjuvant for antigen delivery, as both in vitro as in vivo assays showed higher immune activation compared to free antigen. Conclusions Lyophilization is a promising strategy towards improved stability of protein-loaded microcapsules

Modulation of dendritic cells by lipid grafted polyelectrolyte microcapsules

Polyelectrolyte microcapsules are fabricated by layer-by-layer deposition of dextran sulfate and poly-L-arginine layers at the surface of calcium carbonate template microparticles followed by core removal to produce hollow microcapsules. In the context of vaccination, these biodegradable LbL capsules emerge as promising antigen carriers and are believed to have potential for the co-delivery of antigens and immunomodulators associated within the same particle to enhance and steer the type of immune response. To this end, it is shown that LbL microcapsules can be functionalized at their surface with lipid layers containing immunopotentiators of lipid nature. The potency of the different lipid modified microcapsules to activate dendritic cells (DCs) is demonstrated by increased expression levels of the migration marker CCR7 and the maturation markers CD40 and CD86. Additionally, the DCs cytokine secretion profile is evaluated. The findings reveal that the lipid grafted microcapsules are superior to non-modified microcapsules in DC activation and suggest their potential as immune modulating antigen delivery systems

Polyelectrolyte LbL microcapsules versus PLGA microparticles for immunization with a protein antigen

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