Determination of thickness and density of a wet multilayer polymer system with sub-nanometer resolution by means of a dual polarization silicon-on-insulator microring

Determination of both thickness and refractive index of a thin biomolecular or polymer layer in wet conditions is a task not easily performed. Available tools such as XPS, AFM, ellipsometry and integrated photonic sensors often have difficulties with the native wet condition of said agents-under-test, perform poorly in the sub-5 nm regime or do not determine both characteristics in an absolute simultaneous way. The thickness of a multilayer system is often determined by averaging over a large amount of layers, obscuring details of the individual layers. Even more, the interesting behavior of the first bound layers can be covered in noise or assumptions might be made on either thickness or refractive index in order to determine the other. To demonstrate a solution to these problems, a silicon-on-insulator (SOI) microring is used to study the adsorption of a bilayer polymer system on the silicon surface of the ring. To achieve this, the microring is simultaneously excited with TE and TM polarized light and by tracking the shifts of both resonant wavelengths, the refractive index and the thickness of the adsorbed layer can be determined with a resolution on thickness smaller than 0.1 nm and a resolution on refractive index smaller than 0.01 RIU. An adhesive polyethyleneimine (PEI) layer is adsorbed to the surface, followed by the adsorption of poly(sodium-4-styrene sulfonate) (PSS) and poly(allylamine) hydrochloride (PAH). This high-resolution performance in wet conditions with the added benefits of the SOI microring platform such as low cost and multiplexibility make for a powerful tool to analyze thin layer systems, which is promising to research binding conformation of proteins as well

Feasibility of Mechanical Extrusion to Coat Nanoparticles with Extracellular Vesicle Membranes

Biomimetic functionalization to confer stealth and targeting properties to nanoparticles is a field of intense study. Extracellular vesicles (EV), sub-micron delivery vehicles for intercellular communication, have unique characteristics for drug delivery. We investigated the top-down functionalization of gold nanoparticles with extracellular vesicle membranes, including both lipids and associated membrane proteins, through mechanical extrusion. EV surface-exposed membrane proteins were confirmed to help avoid unwanted elimination by macrophages, while improving autologous uptake. EV membrane morphology, protein composition and orientation were found to be unaffected by mechanical extrusion. We implemented complementary EV characterization methods, including transmission- and immune-electron microscopy, and nanoparticle tracking analysis, to verify membrane coating, size and zeta potential of the EV membrane-cloaked nanoparticles. While successful EV membrane coating of the gold nanoparticles resulted in lower macrophage uptake, low yield was found to be a significant downside of the extrusion approach. Our data incentivize more research to leverage EV membrane biomimicking as a unique drug delivery approach in the near future

The future of layer-by-layer assembly: A tribute to ACS Nano associate editor Helmuth Möhwald

Layer-by-layer (LbL) assembly is a widely used tool for engineering materials and coatings. In this Perspective, dedicated to the memory of ACS Nano associate editor Prof. Dr. Helmuth Möhwald, we discuss the developments and applications that are to come in LbL assembly, focusing on coatings, bulk materials, membranes, nanocomposites, and delivery vehicles

Generic Delivery of Payload of Nanoparticles Intracellularly via Hybrid Polymer Capsules for Bioimaging Applications

Towards the goal of development of a generic nanomaterial delivery system and delivery of the ‘as prepared’ nanoparticles without ‘further surface modification’ in a generic way, we have fabricated a hybrid polymer capsule as a delivery vehicle in which nanoparticles are loaded within their cavity. To this end, a generic approach to prepare nanomaterials-loaded polyelectrolyte multilayered (PEM) capsules has been reported, where polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH) polymer capsules were employed as nano/microreactors to synthesize variety of nanomaterials (metal nanoparticles; lanthanide doped inorganic nanoparticles; gadolinium based nanoparticles, cadmium based nanoparticles; different shapes of nanoparticles; co-loading of two types of nanoparticles) in their hollow cavity. These nanoparticles-loaded capsules were employed to demonstrate generic delivery of payload of nanoparticles intracellularly (HeLa cells), without the need of individual nanoparticle surface modification. Validation of intracellular internalization of nanoparticles-loaded capsules by HeLa cells was ascertained by confocal laser scanning microscopy. The green emission from Tb3+ was observed after internalization of LaF3:Tb3+(5%) nanoparticles-loaded capsules by HeLa cells, which suggests that nanoparticles in hybrid capsules retain their functionality within the cells. In vitro cytotoxicity studies of these nanoparticles-loaded capsules showed less/no cytotoxicity in comparison to blank capsules or untreated cells, thus offering a way of evading direct contact of nanoparticles with cells because of the presence of biocompatible polymeric shell of capsules. The proposed hybrid delivery system can be potentially developed to avoid a series of biological barriers and deliver multiple cargoes (both simultaneous and individual delivery) without the need of individual cargo design/modification

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

Employing a dual polarisation microring to determine refractive index and thickness of a thin polymer layer

Dual polarisation biosensing is a novel optical technique that focuses on retrieving structural information from a bound or adsorbed layer of molecules, by using a silicon-on-insulator (SOI) microring. Both density and thickness of the layer can be monitored simultaneously. Due to a self-calibrating protocol that is quickly performed at the start of every experiment, a high accuracy can be obtained. In this paper, we determine the thickness and refractive index of a thin layer of polyethyleneimine (PEI), which adsorbs to the silicon surface of the microring. This results in a layer with a thickness of 1.158 and a refractive index of 1.453 RIU

Duality of β-glucan microparticles: antigen carrier and immunostimulants

Kim Baert,1 Bruno G De Geest,2 Henri De Greve,3,4 Eric Cox,1,* Bert Devriendt1,* 1Department of Virology, Parasitology and Immunology, 2Department of Pharmaceutics, Ghent University, Merelbeke, Ghent, Belgium; 3Structural Biology Research Centre, VIB, Brussels, Belgium; 4Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium *These authors contributed equally to this work Abstract: Designing efficient recombinant mucosal vaccines against enteric diseases is still a major challenge. Mucosal delivery of recombinant vaccines requires encapsulation in potent immunostimulatory particles to induce an efficient immune response. This paper evaluates the capacity of β-glucan microparticles (GPs) as antigen vehicles and characterizes their immune-stimulatory effects. The relevant infectious antigen FedF was chosen to be loaded inside the microparticles. The incorporation of FedF inside the particles was highly efficient (roughly 85%) and occurred without antigen degradation. In addition, these GPs have immunostimulatory effects as well, demonstrated by the strong reactive oxygen species (ROS) production by porcine neutrophils upon their recognition. Although antigen-loaded GPs still induce ROS production, antigen loading decreases this production by neutrophils for reasons yet unknown. However, these antigen-loaded GPs are still able to bind their specific β-glucan receptor, demonstrated by blocking complement receptor 3, which is the major β-glucan receptor on porcine neutrophils. The dual character of these particles is confirmed by a T-cell proliferation assay. FedF-loaded particles induce a significantly higher FedF-specific T-cell proliferation than soluble FedF. Taken together, these results show that GPs are efficient antigen carriers with immune-stimulatory properties. Keywords: β-glucan microparticles, FedF, antigen delivery vehicle, immunostimulant

Self-exploding lipid-coated microgels

Self-exploding microparticles show potential for advanced delivery of certain therapeutics. This study evaluates (1) whether degrading biodegradable dextran hydroxyethyl methacrylate (dex-HEMA) microgels can be coated by a lipid membrane and (2) whether the surrounding membrane can be ruptured by the increasing swelling pressure of the degrading microgel. We found that adsorption of charged liposomes to oppositely charged dex-HEMA microgels provides efficient coating of the microgels, whereby microparticles with a "core-shell" structure were clearly obtained. Especially, we could confirm experimentally that the swelling pressure increase of degrading dex-HEMA microgels can destroy the lipid membrane surrounding the microgels