In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin

The brain insulin metabolism alteration has been addressed as a pathophysiological factor underlying Alzheimer’s disease (AD). Insulin can be beneficial in AD, but its macro-polypeptide nature negatively influences the chances of reaching the brain. The intranasal (IN) administration of therapeutics in AD suggests improved brain-targeting. Solid lipid nanoparticles (SLNs) and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are promising carriers to deliver the IN-administered insulin to the brain due to the enhancement of the drug permeability, which can even be improved by chitosan-coating. In the present study, uncoated and chitosan-coated insulin-loaded SLNs and PLGA NPs were formulated and characterized. The obtained NPs showed desirable physicochemical properties supporting IN applicability. The in vitro investigations revealed increased mucoadhesion, nasal diffusion, and drug release rate of both insulin-loaded nanocarriers over native insulin with the superiority of chitosan-coated SLNs. Cell-line studies on human nasal epithelial and brain endothelial cells proved the safety IN applicability of nanoparticles. Insulin-loaded nanoparticles showed improved insulin permeability through the nasal mucosa, which was promoted by chitosan-coating. However, native insulin exceeded the blood-brain barrier (BBB) permeation compared with nanoparticulate formulations. Encapsulating insulin into chitosan-coated NPs can be beneficial for ensuring structural stability, enhancing nasal absorption, followed by sustained drug release.     

Preparation of transparent conductive indium tin oxide thin films from nanocrystalline indium tin hydroxide by dip-coating method

Indium tin oxide (ITO) thin films with well-controlled layer thickness were produced by dip-coating method. The ITO was synthesized by a sol-gel technique involving the use of aqueous InCl₃, SnCl₄ and NH₃ solutions. To obtain stable sols for thin film preparation, as-prepared Sn-doped indium hydroxide was dialyzed, aged, and dispersed in ethanol. Polyvinylpyrrolidone (PVP) was applied to enhance the stability of the resulting ethanolic sols. The transparent, conductive ITO films on glass substrates were characterized by X-ray diffraction, scanning electron microscopy and UV-Vis spectroscopy. The ITO layer thickness increased linearly during the dipping cycles, which permits excellent controllability of the film thickness in the range ~ 40-1160 nm. After calcination at 550 °C, the initial indium tin hydroxide films were transformed completely to nanocrystalline ITO with cubic and rhombohedral structure. The effects of PVP on the optical, morphological and electrical properties of ITO are discussed.     

Conserved and Distinct Elements of Phagocytosis in Human and C. elegans

Endocytosis provides the cellular nutrition and homeostasis of organisms, but pathogens often take advantage of this entry point to infect host cells. This is counteracted by phagocytosis that plays a key role in the protection against invading microbes both during the initial engulfment of pathogens and in the clearance of infected cells. Phagocytic cells balance two vital functions: preventing the accumulation of cell corpses to avoid pathological inflammation and autoimmunity, whilst maintaining host defence. In this review, we compare elements of phagocytosis in mammals and the nematode Caenorhabditis elegans. Initial recognition of infection requires different mechanisms. In mammals, pattern recognition receptors bind pathogens directly, whereas activation of the innate immune response in the nematode rather relies on the detection of cellular damage. In contrast, molecules involved in efferocytosis—the engulfment and elimination of dying cells and cell debris—are highly conserved between the two species. Therefore, C. elegans is a powerful model to research mechanisms of the phagocytic machinery. Finally, we show that both mammalian and worm studies help to understand how the two phagocytic functions are interconnected: emerging data suggest the activation of innate immunity as a consequence of defective apoptotic cell clearance.     

Effect of the solid precursors on the formation of nanosized TiBx powders in RF thermal plasma

Continuous synthesis of TiB_x (x≈0.5–2) nanoparticles from various low cost solid precursors such as titanium and titanium dioxide admixed with boron and/or carbon in radiofrequency thermal plasma was studied. Feasibility of TiB₂ formation was predicted by thermodynamic equilibrium calculations in the 500–5000 K temperature range. In all the investigated system high temperature reactions resulted in nanometer-sized TiB_x powders with a mean size varying between 13 and 83 nm. The yield of particular runs ranged from 38% to 97%. Among the synthesized products in addition to TiB_x, oxidized precursor residues were also found in smaller quantities. Although addition of carbon to the precursors could not completely prevent surface oxidation of boride particles, it contributed to the reduction of the mean particle size of the formed TiB₂.     

A short solid-state synthesis leading to titanate compounds with porous structure and nanosheet morphology

A novel method was developed for the synthesis of titanate nanosheets with high surface area. A solid-state mixture of NaOH and TiO₂ was reacted at 600 °C for several minutes. The aqueous dispersion of the resulting melt was aged at room temperature for periods up to 14 days. After hydrochloric acid treatment and washing procedures, the reaction product was characterized by X-ray diffraction, Raman spectroscopy, N₂-sorption and small-angle X-ray scattering measurements. The titanate compound not subjected to the aging process was amorphous and possessed a microporous framework, while the aged samples displayed nanosheet morphology and high specific surface area (396-509 m² g⁻¹). It was revealed that the very short heat treatment is of crucial importance for the titania-titanate phase transformation, while the aging process is needed for the morphological evolution of the titanate samples. The effects of the aging time on the structure and the morphology are discussed.     

Optimization of Lyophilized Hyperacute Serum (HAS) as a Regenerative Therapeutic in Osteoarthritis

Hyperacute serum (HAS) is a blood derivative product that promotes the proliferation of various cell types and controls inflammation in vitro. The aim of this study is to investigate the regenerative potential of different formulations of HAS, including lyophilized and hyaluronic acid combined versions, to obtain a stable and standardized therapeutic in osteoarthritis (OA), which may be able to overcome the variability limitations of platelet-rich plasma (PRP). Primary human osteoarthritic chondrocytes were used for testing cellular viability and gene expression of OA-related genes. Moreover, a co-culture of human explants of cartilage, bone and synovium under inflammatory conditions was used for investigating the inflammatory control capacities of the different therapeutics. In this study, one formulation of lyophilized HAS achieved the high cell viability rates of liquid HAS and PRP. Gene expression analysis showed that HAS induced higher Col1a1 expression than PRP. Cytokine quantification from supernatant fluids revealed that HAS treatment of inflamed co-cultures significantly reduced levels of IL-5, IL-15, IL-2, TNFα, IL-7 and IL-12. To conclude, lyophilized HAS is a stable and standardized therapeutic with high potential in joint regeneration.     

Leaching of antimony from polyethylene terephthalate (PET) bottles into mineral water

The Sb leaching from polyethylene terephthalate (PET) package material into 10 different brands of still (non-carbonated) and sparkling (carbonated) Hungarian mineral water purchased in supermarkets was investigated by inductively coupled plasma sector field mass spectrometry (ICP-SF-MS). The Sb concentration measured in PET package materials varied between 210 and 290 mg/kg. Generally, the Sb concentration of still mineral water was lower than that of sparkling in the case of identical storage time. For modelling improper storage conditions, storage time (10-950 days), temperature (22 °C-70 °C), illumination (dark vs. 23 W daylight lamp for 116 h) as well as bottle volume (0.5, 1.0 and 1.5 L) were taken into consideration. Under certain extreme light and temperature storage conditions, the Sb concentration of some samples exceeded the concentration value of 2 ng/mL. The extent of Sb leaching from the PET recipients of different brands of mineral water can differ by even one order of magnitude in experiments conducted under the same conditions. Thus, the adequate selection of the polymer used for the production of the PET bottle for the solar water disinfection (SODIS) procedure seems to ensure low Sb levels in the water samples.     

Microbial population in a hydrogen-dependent denitrification reactor

The bacterial population in an H2-dependent denitrification system was studied. The laboratory set-up was designed for the treatment of potable water and consisted of an electrochemical cell, where the water to be treated was enriched with H2 prior to entering a bioreactor. Bioreactors (columns packed with granulated active carbon) were inoculated with denitrifying bacterial strains isolated from a previous reactor, then sampled immediately after inoculation, or after 1 or 3 months of continuous operation. Total number of the bacteria and numbers of each different strain were determined at various levels of the bioreactor. The strains present in the inoculum were identified as Ochrobactrum anthropi, Pseudomonas stutzeri, Paracoccus panthotrophus and Paracoccus denitrificans. Numbers of the latter declined markedly with time with the other three strains being responsible for nitrate removal. A correlation was found between the relative abundance of each strain and its specific denitrification activity.     

Factor XIII B Subunit Polymorphisms and the Risk of Coronary Artery Disease

The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.