Polymeric multilayer capsules have emerged as a novel drug delivery platform. These capsules are fabricated through layer-by-layer sequential deposition of polymers onto a sacrificial core template followed by the decomposition of this core yielding hollow capsules. The resulting nanometer thin membrane is permselective, allowing diffusion of water and ions but excluding larger molecules. Moreover, the sequential fabrication procedure allows a precise fine-tuning of the capsules physicochemical and biological properties. These properties have put polymeric multilayer capsules under major attention in the field of drug delivery. In this review we focus on polymeric multilayer capsule mediated delivery of biotechnological macromolecular drugs such as peptides, proteins and nucleic acids.
Polyelectrolyte multilayer capsules have recently gained interest as carriers for drug delivery. When envisioning mucosal administration, one is focused with potential concerns such as tissue irritation and tissue damage, induced by the carrier itself. In this paper we demonstrate the use of a slug-based (Arion lusitanicus) assay to evaluate the mucosal irritation potential of different types of polyelectrolytes, their complexes and multilayer capsules. This assay allows to assess in a simple yet efficient way mucosal tissue irritation without using large numbers of vertebrates such as mice, rabbits or non-human primates. We found that although single polyelectrolyte components do induce tissue irritation, this response is dramatically reduced upon complexation with an oppositely charged polyelectrolyte, rendering fairly inert polyelectrolyte complexes. These findings put polyelectrolyte multilayer capsules further en route towards drug delivery applications.
Recent advances in medicine and biotechnology have prompted the need to develop nanoengineered delivery systems that can encapsulate a wide variety of novel therapeutics such as proteins, chemotherapeutics, and nucleic acids. Moreover, these delivery systems should be "intelligent", such that they can deliver their payload at a well-defined time, place, or after a specific stimulus. Polymeric multilayer capsules, made by layer-by-layer (LbL) coating of a sacrificial template followed by dissolution of the template, allow the design of microcapsules in aqueous conditions by using simple building blocks and assembly procedures, and provide a previously unmet control over the functionality of the microcapsules. Polymeric multilayer capsules have recently received increased interest from the life science community, and many interesting systems have appeared in the literature with biodegradable components and biospecific functionalities. In this Review we give an overview of the recent breakthroughs in their application for drug delivery.
Aortic heart valve disease is a growing health problem and a tissue-engineered aortic heart valve could be a promising therapy. In this paper, decellularized porcine aortic heart valve leaflets are used as scaffolds and loaded with growth factor and heparin via layer-by-layer electrostatic deposition (LbL technique) with the final purpose to stimulate and control cellular processes. Binding and subsequent release of heparin and basic fibroblast growth factor (bFGF) from aortic valve leaflets were assessed qualitatively by immunohistochemistry and quantitatively by radioactive labeling methods. It was observed that the amount of heparin and bFGF bound to aortic heart valve leaflets was directly proportional to the concentration of heparin and bFGF in the incubation medium. Release of heparin and bFGF from the decellularized heart valve leaflets at physiological conditions was sustained over 4 days while preserving the biological activity of the released growth factor.
Polyelectrolyte microcapsules were prepared by the layer-by-layer assembly of hyaluronic acid (HA) and a polycationic polymer, poly(allylamine) (PAH) or poly(lysine) (PLL). The influence of the polycationic partner on the morphology, stability, permeability properties, and enzymatic degradation of microcapsules was thoroughly analyzed. It was found that these properties could be tuned by shell cross-linking. Confocal microscopy studies of cellular uptake of the capsules showed that the polyelectrolyte shells remain stable outside the cells but readily break open once internalized by cells, suggesting their potential as carrier for intracellular drug delivery.
A Michael addition strategy involving the reaction between a maleimide double bond and amine groups is investigated for the synthesis of cryogels at subzero temperature. Low-molecular-weight PEG-based building blocks with amine end groups and disulfide-containing building blocks with maleimide end groups are combined to synthesize redox-responsive PEG cryogels. The cryogels exhibit an interconnected macroporous morphology, a high compressive modulus and gelation yields of around 95%. While the cryogels are stable under physiological conditions, complete dissolution of the cryogels into water-soluble products is obtained in the presence of a reducing agent (glutathione) in the medium. Cell seeding experiments and toxicologic analysis demonstrate their potential as scaffolds in tissue engineering.
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