Modified activities of macrophages' deubiquitinating enzymes after infection.

influences several host molecular/signaling pathways during infection. Ubiquitination and deubiquitination are among the most important regulatory mechanisms and respectively occur through attachment or removal of the ubiquitin molecule. The process is necessary not only to mark molecules for degradation, but also, for example, to the activation of signaling pathways leading to pro-inflammatory host response.

Surprising efficacy twist of two established cytostatics revealed by a-la-carte 3D cell spheroid preparation protocol.

Three-dimensional cell culture systems are increasingly used for biological and anticancer drug screening as they mimic the structure and microenvironment of tumors more closely than conventional two-dimensional cell models. In this study, the growth kinetics of colon adenocarcinoma-derived spheroids (HT-29 cell line) cultivated in liquid marble micro-bioreactors and nonadherent PDMS-coated well plates was investigated in detail and enabled precise control of the spheroid size by the seed cell density and cultivation time. The therapeutic effect of 5-fluorouracil and irinotecan hydrochloride in 2D monolayer cell culture and 3D tumor spheroids revealed an unexpected twist in their efficacy due to different ability to penetrate through 3D microtissue.

Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington's Disease and Human Blood Plasma.

(1) Background: Huntington's disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies.

Evaluation of β-glucan particles as dual-function carriers for poorly soluble drugs.

Yeast glucan particles are porous polysaccharide cell walls extracted from Saccharomyces cerevisiae. Being mildly immunogenic, they are efficiently phagocytosed and have therefore been proposed as possible vehicles for drug delivery. Using curcumin as a model poorly water-soluble drug, a systematic comparison of three different physical loading methods - incipient wetness impregnation, slurry evaporation, and spray drying - was carried out and their influence on the particle morphology, encapsulation efficiency, amorphous drug content and release kinetics was evaluated.

The effect of curcumin encapsulation into yeast glucan particles on antioxidant enzyme expression .

Glucan particles (GPs) from Saccharomyces cerevisiae consist mainly of β-1,3-d-glucan. Curcumin is a phenolic compound of plant origin. A 24 h incubation with a mixture of GPs and curcumin increased the expression of the Nrf2 protein and increased the activation of the Nrf2-ARE system significantly.

Incorporating natural anti-inflammatory compounds into yeast glucan particles increases their bioactivity in vitro.

Yeast glucan particles (GPs) are promising agents for the delivery of biologically active compounds as drugs. GPs possess their own biological activities and can act synergistically with their cargo. This study aimed to determine how incorporating artemisinin, ellagic acid, (-)-epigallocatechin gallate, morusin, or trans-resveratrol into GPs affects their anti-inflammatory and antioxidant potential in vitro.

Composites of yeast glucan particles and curcumin lead to improvement of dextran sulfate sodium-induced acute bowel inflammation in rats.

The goal of this work was to assess the usability of yeast glucan particles (GPs) as carriers for curcumin and determine the beneficial effect of a pharmacological composite of curcumin in GPs on dextran sulfate sodium induced colitis in rats. The assessment of the anti-inflammatory effect of particular substances was evaluated on the basis of the calculated disease activity index and by assessment of cytokines and enzymes from the gut tissue - tumor necrosis factor α (TNF-α), transforming growth factor β1, interleukin (IL)-1β, IL-6, IL-10, IL-17, catalase, superoxide dismutase 2, myeloperoxidase (MPO), and matrix metalloproteinase 9. Composites of GPs with incorporated curcumin showed promising results with the capability to lower symptoms of colitis and significantly decrease the production of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and the activity of MPO, as well.

Anti-inflammatory potential of composites of yeast glucan particles and geranylated flavonoid diplacone.

Geranylated flavanone diplacone is a flavanone iso- lated from Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae) with anti-inflammatory and antioxidant properties, nevertheless showing high lipophilicity and low solubility in water.

Glucan particles as suitable carriers for the natural anti-inflammatory compounds curcumin and diplacone - Evaluation in an ex vivo model.

Natural compounds offer a wide spectrum of potential active substances, but often they have a poor bioavailability. To increase the bioavailability and bioactivity of the natural anti-inflammatory molecules curcumin and diplacone, we used glucan particles (GPs), hollow shells from Saccharomyces cerevisiae composed mainly of β-1,3-d-glucan. Their indigestibility and relative stability in the gut combined with their immunomodulatory effects makes them promising carriers for such compounds.

Encapsulation of poorly soluble drugs in yeast glucan particles by spray drying improves dispersion and dissolution properties.

In this work, novel amorphous solid dispersions based on yeast glucan particles were produced. Yeast glucan particles are hollow and porous, and they are mainly composed of amorphous polysaccharides. We hypothesized that these particles are suitable candidates for the amorphization of drugs with low water solubility.

Curcumin encapsulation in yeast glucan particles promotes its anti-inflammatory potential in vitro.

Glucan particles (GPs) from Saccharomyces cerevisiae are hollow shells that are composed mainly of β-1,3-d-glucan, which has demonstrated immunomodulatory and anti-inflammatory potential both in vitro and in vivo. Curcumin is a natural hydrophobic phenolic compound, which possesses a significant anti-inflammatory effect and is used as supportive therapy in the treatment of many inflammatory diseases. The aim of this study is to evaluate the possible synergic effect and other benefits of the co-application of GPs and curcumin in the form of pharmaceutical composites.

Magnetically Controlled Liposome Aggregates for On-Demand Release of Reactive Payloads.

A colloidal system able to act as a miniature reactor for on-demand release of reactive payloads has been demonstrated. The system is based on submicrometer aggregates consisting of anionic liposomes that act as storage reservoirs for the reactants, superparamagnetic iron oxide nanoparticles (SPIONs) that enable magnetic positioning in space and controlled release of reactants from the liposomes by radiofrequency stimulation, and an oppositely charged polyelectrolyte (poly-l-lysine) that keeps the constituent elements within the aggregates at a defined ratio. The kinetics of liposome-PLL-SPION heteroaggregation was systematically mapped and a suitable composition of the liposome bilayer was found such that the system exhibits stability at ambient conditions and radiofrequency triggered release at physiological temperature.

Effect of lipid nanoparticle formulations on skin delivery of a lipophilic substance.

The aim of this study was to follow the skin penetration of a model lipophilic compound (Nile red) delivered by nanoparticulate carriers, the so-called lipid nanocapsules. The nanocapsules consisting of an oil core stabilized by amixture of surfactants were prepared by the phase inversion temperature method. Varying the particle composition (the oil/surfactant ratio) nanoparticles of different size were prepared and characterized.

Nanocrystals for dermal penetration enhancement - Effect of concentration and underlying mechanisms using curcumin as model.

Nanocrystals have received considerable attention in dermal application due to their ability to enhance delivery to the skin and overcome bioavailability issues caused by poor water and oil drug solubility. The objective of this study was to investigate the effect of nanocrystals on the mechanism of penetration behavior of curcumin as a model drug. Curcumin nanocrystals were produced by the smartCrystals® process, i.

Non-invasive insight into the release mechanisms of a poorly soluble drug from amorphous solid dispersions by confocal Raman microscopy.

In this study, we investigated the release mechanism of the poorly water soluble drug aprepitant from different amorphous solid dispersions using confocal Raman microscopy (CRM). Solid dispersions were fabricated based on either Soluplus®, as an amphiphilic copolymer and solubilizer, or on polyvinylpyrrolidone, as a hydrophilic polymer, in order to elucidate the influence of the polymer characteristics on the drug form and dissolution mechanisms. Aprepitant exhibited its amorphous form in both solid dispersions.

Biologically triggered liberation of sub-micron particles from alginate microcapsules.

A new method for triggering the burst liberation of encapsulated sub-micron particles from carrier particles using embedded microorganisms has been developed. Triggering mechanisms such as those based on chemical, light, thermal, or magnetic stimuli are known, but man-made particles are not yet able to replicate the concept of "dormancy" found in biological systems in the form of spores or seeds that survive in an inactive state and start to grow only once favourable environmental conditions are encountered. An engineered particle system that mimics this property by embedding viable yeast cells into synthetically made alginate microcapsules is reported in the present work.

Remotely controlled diffusion from magnetic liposome microgels.

The reversible, temperature-dependent change in the permeability of a phospholipid bilayer has been used for controlling the diffusion rate of encapsulated molecular payload from liposomes. Liposomes were preloaded with a fluorescent dye and immobilized in calcium alginate hydrogel microparticles that also contained iron oxide nanoparticles. The composite microparticles were produced by a drop-on-demand inkjet method.

Encapsulation stability and temperature-dependent release kinetics from hydrogel-immobilised liposomes.

Composite microparticles consisting of a calcium alginate gel matrix with embedded liposomes made from cholesterol:DPPC (dipalmitoylphosphatidylcholine) mixtures were considered. Factors affecting the encapsulation stability of liposomes during the gel formation by ionic cross-linking--namely temperature and the cholesterol:DPPC ratio--were systematically investigated. The liposomes were found to be tolerant to Ca(2+) ions during cross-linking of the gel and stable in the hydrogel matrix for extended periods of time when cholesterol was present in the phospholipid bilayer and temperature was kept sufficiently below the phase transition.

Reversible buckling and diffusion properties of silica-coated hydrogel particles.

The structure and diffusion properties of composite particles consisting of a calcium alginate hydrogel core and a thin SiO(2) surface layer have been investigated. The composite particles were formed by depositing a silica layer onto calcium alginate cores using a sol-gel process starting from alkoxysilane precursors. The composite particles were found to have a remarkable ability to reversibly rehydrate and return to their original size and shape after partial drying.

Investigation of internal microstructure and thermo-responsive properties of composite PNIPAM/silica microcapsules.

Composite microcapsules consisting of a thermo-responsive hydrogel poly-N-isopropylacrylamide (PNIPAM) and coated by silica (SiO(2)) nanoparticles have been synthesized by the inverse Pickering emulsion polymerization method. The composite capsules, whose mean diameter is in the 25-86 microm range in the expanded state, were characterized by static light scattering, atomic force microscopy (AFM), scanning electron microscopy (SEM), and laser scanning confocal microscopy (LSCM). It is reported that the hydrogel surface is uniformly covered by a monolayer of silica nanoparticles and that depending on the capsule size and degree of polymer cross-linking, either hollow-core or partially-filled hydrogel-core microcapsules can be created.

The xyloglucan-cellulose assembly at the atomic scale.

The assembly of cell wall components, cellulose and xyloglucan (XG), was investigated at the atomistic scale using molecular dynamics simulations. A molecular model of a cellulose crystal corresponding to the allomorph Ibeta and exhibiting a flexible complex external morphology was employed to mimic the cellulose microfibril. The xyloglucan molecules considered were the three typical basic repeat units, differing only in the size of one of the lateral chain.