Agar Graft Modification with Acrylic and Methacrylic Acid for the Preparation of pH-Sensitive Nanogels for 5-Fluorouracil Delivery.

Agar, a naturally occurring polysaccharide, has been modified by grafting it with acrylic (AcA) and methacrylic (McA) acid monomers, resulting in acrylic or methacrylic acid grafted polymer (AA-g-AcA or AA-g-McA) with pH-sensitive swelling behavior. Different ratios between agar, monomers, and initiator were applied. The synthesized grades of both new polymer series were characterized using FTIR spectroscopy, NMR, TGA, DSC, and XRD to ascertain the intended grafting. The percentage of grafting (% G), grafting efficiency (% GE), and % conversion (% C) were calculated, and models with optimal characteristics were further characterized. The swelling behavior of the newly synthesized polymers was studied over time and in solutions with different pH. These polymers were subsequently crosslinked with varying amounts of glutaraldehyde to obtain 5-fluorouracil-loaded nanogels. The optimal ratios of polymer, drug, and crosslinker resulted in nearly 80% loading efficiency. The performed physicochemical characterization (TEM and DLS) showed spherical nanogels with nanometer sizes (105.7-250 nm), negative zeta potentials, and narrow size distributions. According to FTIR analysis, 5-fluorouracil was physically incorporated. The swelling and release behavior of the prepared nanogels was pH-sensitive, favoring the delivery of the chemotherapeutic to tumor cells. The biocompatibility of the proposed nanocarrier was proven using an in vitro hemolysis assay.

Thermosensitive Hydrogel-Functionalized Mesoporous Silica Nanoparticles for Parenteral Application of Chemotherapeutics.

Hydrogels can offer many opportunities for drug delivery strategies. They can be used on their own, or their benefits can be further exploited in combination with other nanocarriers. Intelligent hydrogels that react to changes in the surrounding environment can be utilized as gatekeepers and provide sustained on-demand drug release. In this study, a hybrid nanosystem for temperature- and pH-sensitive delivery was prepared from MCM-41 nanoparticles grafted with a newly synthesized thermosensitive hydrogel (MCM-41/AA-g-PnVCL). The initial particles were chemically modified by the attachment of carboxyl groups. Later, they were grafted with agar (AA) and vinylcaprolactam (VCL) by free radical polymerization. Doxorubicin was applied as a model hydrophilic chemotherapeutic drug. The successful formulation was confirmed by FT-IR and TGA. Transmission electron microscopy and dynamic light scattering analysis showed small particles with negative zeta potential. Their release behaviour was investigated in vitro in media with different pH and at different temperatures. Under tumour simulating conditions (40 °C and pH 4.0), doxorubicin was almost completely released within 72 h. The biocompatibility of the proposed nanoparticles was demonstrated by in vitro haemolysis assay. These results suggest the possible parenteral application of the newly prepared hydrogel-functionalized mesoporous silica nanoparticles for temperature-sensitive and pH-triggered drug delivery at the tumour site.

Doxorubicin and Quercetin Double Loading in Modified MCM-41 Lowered Cardiotoxicity in H9c2 Cardioblast Cells In Vitro.

BACKGROUND: One of the therapeutic limitations of the use of doxorubicin (DOX) as an anticancer drug is its cardiotoxicity. Its hydrophilicity also causes difficulties in achieving sustained release. The simultaneous delivery with the well-known natural antioxidant quercetin could ameliorate its cardiotoxicity. Thus, the main aim of this work is to study the potential of carboxylated and non-carboxylated mesoporous silica MCM-41 nanoparticles for double loading of the hydrophilic doxorubicin hydrochloride and hydrophobic quercetin (Q) in one nanocarrier with a modified release pattern to reduce the cardiotoxic side effects of doxorubicin in vitro. METHODS: The methods included the modification of MCM-41, single and double loading of modified and non-modified MCM-41, physicochemical characterization, in vitro release tests and kinetic study, and in vitro cell viability studies. RESULTS: Doxorubicin and quercetin were successfully double-loaded with encapsulation efficiency (EE) of 43 ± 4.1% and 37 ± 4.5%, respectively, in native MCM-41. The post-synthetic carboxylation led to 49 ± 4.3% EE (DOX) and 36 ± 4.0% (Q) and double lowering of the cardiotoxicity on H9c2 (IC50 = 5.96 µm). Sustained release profiles over 72 h were achieved. CONCLUSIONS: A successful procedure was proposed for the efficient double loading of a hydrophilic drug and a hydrophobic drug. The carboxy-modified double-loaded nanosystems demonstrate a decreased in vitro cardiotoxicity of doxorubicin and can be considered as a potential chemotherapeutic formulation.

Influence of growth structures and fixed appliances on automated cephalometric landmark recognition with a customized convolutional neural network.

BACKGROUND: One of the main uses of artificial intelligence in the field of orthodontics is automated cephalometric analysis. Aim of the present study was to evaluate whether developmental stages of a dentition, fixed orthodontic appliances or other dental appliances may affect detection of cephalometric landmarks. METHODS: For the purposes of this study a Convolutional Neural Network (CNN) for automated detection of cephalometric landmarks was developed. The model was trained on 430 cephalometric radiographs and its performance was then tested on 460 new radiographs. The accuracy of landmark detection in patients with permanent dentition was compared with that in patients with mixed dentition. Furthermore, the influence of fixed orthodontic appliances and orthodontic brackets and/or bands was investigated only in patients with permanent dentition. A t-test was performed to evaluate the mean radial errors (MREs) against the corresponding SDs for each landmark in the two categories, of which the significance was set at p < 0.05. RESULTS: The study showed significant differences in the recognition accuracy of the Ap-Inferior point and the Is-Superior point between patients with permanent dentition and mixed dentition, and no significant differences in the recognition process between patients without fixed orthodontic appliances and patients with orthodontic brackets and/or bands and other fixed orthodontic appliances. CONCLUSIONS: The results indicated that growth structures and developmental stages of a dentition had an impact on the performance of the customized CNN model by dental cephalometric landmarks. Fixed orthodontic appliances such as brackets, bands, and other fixed orthodontic appliances, had no significant effect on the performance of the CNN model.

Gel Formulations for Topical Treatment of Skin Cancer: A Review.

Skin cancer, with all its variations, is the most common type of cancer worldwide. Chemotherapy by topical application is an attractive strategy because of the ease of application and non-invasiveness. At the same time, the delivery of antineoplastic agents through the skin is difficult because of their challenging physicochemical properties (solubility, ionization, molecular weight, melting point) and the barrier function of the stratum corneum. Various approaches have been applied in order to improve drug penetration, retention, and efficacy. This systematic review aims at identifying the most commonly used techniques for topical drug delivery by means of gel-based topical formulations in skin cancer treatment. The excipients used, the preparation approaches, and the methods characterizing gels are discussed in brief. The safety aspects are also highlighted. The combinatorial formulation of nanocarrier-loaded gels is also reviewed from the perspective of improving drug delivery characteristics. Some limitations and drawbacks in the identified strategies are also outlined and considered within the future scope of topical chemotherapy.

Research of Water Molecules Cluster Structuring during Haberlea rhodopensis Friv. Hydration.

Gesneriaceae plant family is comprised of resurrection species, namely Boea hygrometrica and Paraboea rufescens, that are native to the Southeast Asia and Haberlea rhodopensis, Ramonda myconi, and Ramonda serbica, which are mainly found in the Balkan Peninsula. Haberlea rhodopensis is known to be able to survive extreme and prolonged dehydration. Study was carried out after the dried plant Haberlea rhodopensis Friv. had been hydrated and had reached its fresh state. Two juice samples were collected from the plant blossom: The first sample was prepared with 1% filtered water through a patented EVOdrop device. Then the sample was saturated with hydrogen with EVOdrop booster to a concentration of 1.2 ppm, pH = 7.3, ORP = -390 mV. This first sample was prepared with filtered tap water from Sofia, Bulgaria. The second sample, which was a control one, was developed with tap water from Sofia, Bulgaria, consisting of 1% solutions of Haberlea rhodopensis. A study revealed that during the drying process in H. rhodopensis the number of free water molecules decreases, and water dimers are formed. The aim of our study was to determine the number of water molecules in clusters in 1% solutions of hydrated H. rhodopensis plants. Results were analyzed according to the two types of water used in the experiment. Th EVOdrop device is equipped with an ultranano membrane and rotating jet nozzle to create a vortex water and saturation thanks to a second device EVObooster to obtain hydrogen-rich water. In the current study Hydrogen-rich water is referred to as Hydrogen EVOdrop Water (HEW). Research was conducted using the following methods-spectral methods non-equilibrium energy spectrum (NES) and differential non-equilibrium energy spectrum (DNES), mathematical models, and study of the distribution of water molecules in water clusters. In a licensed Eurotest Laboratory, the research of tap water before and after flowing through the EVOdrop device was proven. Studies have been carried out on the structuring of water molecule clusters after change of hydrogen bond energies. The restructuring comes with rearrangement of water molecules by the energy levels of hydrogen bonds. Local extrema can be observed in the spectrum with largest amount of water molecules. The structural changes were tested using the NES and DNES spectral methods. The conducted research proved that the application of EVOdrop device and EVObooster changes the parameters of water to benefit hydration and health.

Sonochemically engineered nano-enabled zinc oxide/amylase coatings prevent the occurrence of catheter-associated urinary tract infections.

Catheter-associated urinary tract infections (CAUTIs), caused by biofilms, are the most frequent health-care associated infections. Novel antibiofilm coatings are needed to increase the urinary catheters' life-span, decrease the prevalence of CAUTIs and reduce the development of antimicrobial resistance. Herein, antibacterial zinc oxide nanoparticles (ZnO NPs) were decorated with a biofilm matrix-degrading enzyme amylase (AM) and simultaneously deposited onto silicone urinary catheters in a one-step sonochemical process. The obtained nano-enabled coatings inhibited the biofilm formation of Escherichia coli and Staphylococcus aureus by 80% and 60%, respectively, for up to 7 days in vitro in a model of catheterized bladder with recirculation of artificial urine due to the complementary mode of antibacterial and antibiofilm action provided by the NPs and the enzyme. Over this period, the coatings did not induce toxicity to mammalian cell lines. In vivo, the nano-engineered ZnO@AM coated catheters demonstrated lower incidence of bacteriuria and prevent the early onset of CAUTIs in a rabbit model, compared to the animals treated with pristine silicone devices. The nano-functionalization of catheters with hybrid ZnO@AM coatings appears as a promising strategy for prevention and control of CAUTIs in the clinic.

Meat of South American camelids - Sensory quality and nutritional composition.

Meat contains a range of nutrients in a highly bioavailable form and when meat is excluded from the diet, without being replaced with suitable alternatives, nutrient deficiencies may occur. For this reason, it is very important to extend our knowledge of nutrients in alternative red meats, such as that provided from the South American camelids- llama and alpaca. This review summarises the current information on the nutritional and sensory parameters of llama and alpaca meat and factors affecting quality. South American camelids produce lean carcases, with an uneven fat distribution across the carcase. Llama and alpaca meat quality traits are mostly influenced by animal nutrition, animal age and processing methods. A feeding strategy based on pasture and hay supplement of barley and alfalfa, and processing younger animals (18 months) has improved the fatty acid composition respectively in llama and alpaca meat, whereas meat colour and tenderness are influenced by processing treatments including electrical stimulation, tenderstretching and enzymatic infusion.

Genetic characterization of silkworm (Bombyx mori L. ) strains (Lepidoptera: Bombicidae) with different geographical originon the basis of isozyme markers

The aim of the present study was to assess genetics variations within and among strains with different geographical origin, belonging to Bulgarian germplasm bank of mulberry silkworm (Bombyx moriL.)and to establish their relationships using isoenzyme markers. Polyacrilamide gel electrophoresis (PAGE) was used to study the isoenzymes of nonspecific esterases (EST), malate dehydrogenase (MDH) and acid phosphatase (ACP) from haemolymph, phosphoglucomutase (PGM) and hexokinase (HK) from silk glands and alkaline phosphatase (ALP) from midgut of mulberry silkworm (Bombyx moriL.). Variability was evident in all of these enzyme systems among twelve strains from Bulgarian germplasm resources of B. mori.Total of nine lociwere detected. All of them (100%) were polymorphic. “Null” alleles in four lociwere determined. Intra-and inter-strain polymorphism was obtained. The degree of polymorphism ranged from 0% to 77.80%. Low levels of observed heterozygosity in comparison with the expected one have been calculated in almost all of strainsas well as deviations from Hardy-Weinberg equilibrium in almost all analyzed loci, resultingof excess of homozygotes. The value of FSTwas 0.4903. The dendrogram constructed with the values of genetic distance manifests that Romanian strain Cislau Tokay is formed one main clade while the rest strains studied (from Bulgaria, Japan, China, Vietnam, Spain, Syria and Egypt) are formed the other clade withsubclades. The genetic data of the tested strains from different geographical regions, would be used for identifying suitable parents for breeding programs with a view to yield improvement in this species with economic significance.

Risk assessment of some heavy metals in mussels (Mytilus galloprovincialis) and veined rapa whelks (Rapana venosa) for human health.

The purpose of the present study was to analyze the concentrations of lead, cadmium and mercury in mussels (Mytilus galloprovincialis) and veined rapa whelks (Rapana venosa) caught in the Varna Bay of Black Sea and to evaluate the risk for human health from the presence of the three heavy metals. The highest average concentrations in mussels were those of cadmium (0.280 mg/kg), followed by lead (0.251 mg/kg) and mercury (0.017 mg/kg). Veined rapa whelks also showed highest levels of cadmium (1.113 mg/kg), followed by lead (0.045 mg/kg) and mercury (0.034 mg/kg). EDI values for adults consuming mussels and veined rapa whelks were below the published RfDo and PTWI values. All THQ and HI values were below 1. The consumption of M. galloprovincialis and R. venosa caught in the Varna Bay, Black Sea, did not pose any risk for the health of adult people as lead, cadmium and mercury were concerned.