Bioactive Glass Nanoparticles as a New Delivery System for Sustained 5-Fluorouracil Release: Characterization and Evaluation of Drug Release Mechanism

Bioactive glass nanoparticles were synthesized and tested for the first time as a new delivery system for sustained 5-fluorouracil (5-FU) release. They were characterized by TEM, DTA, TGA, and FT-IR. The porosity % and specific surface area of glass nanoparticles were 85.59% and 378.36 m2/g, respectively. The in vitro bioactivity evaluation confirmed that bioactive glass disks prepared from these nanoparticles could induce hydroxyapatite layer over their surfaces in simulated body fluid. The in vitro drug release experiment indicated that glass nanoparticles could serve as long-term local delivery vehicles for sustained 5-FU release. The release profile of 5-FU showed an initial fast release stage followed by a second stage of slower release. The initial burst release of 5-FU in the first day was about 23% (28.92 mg·L−1) of the total amount of loaded 5-FU, while the final cumulative percentage of the 5-FU released after 32 days was about 45.6% (57.31 mg·L−1) of the total amount of loaded 5-FU. The application of different mathematical models indicated that 5-FU was released by diffusion controlled mechanism and suggested that its release rate was dependent on glass particles dissolution, changes of surface area as well as diameter of glass particles, and concentration of loaded drug

Molecular characterization of cytochrome P450 1B1 and effect of benzo(a) pyrene on its expression in Nile tilapia (Oreochromis niloticus)

Cytochrome P4501 (CYP1) family enzymes are most active in hydroxylating a variety of environmental contaminants including Polyaromatic Hydrocarbons (PAH), planar polychlorinated biphenyls and arylamines. CYP1B which belongs to the cytochrome  P450 superfamily of genes, is involved in the oxidation of endogenous and exogenous compounds, and could potentially be a useful biomarker in fish for exposure to arylhydrocarbon receptors (AhR) ligands. In this study, a new complementary   DNA (cDNA) of the CYP1B subfamily encoding 1B1 was isolated from Nile tilapia (Oreochromis niloticus) liver after intracoelomic injection with benzo (a) pyrene (BaP). The full-length cDNA was 2107 base pair (bp) long and contained a 5' noncoding region of 29 bp, an open reading frame of 1527 bp coding for 508 amino acids and a stop codon, and a 3' noncoding region of 551 bp, respectively. The deduced amino acid sequence of Nile tilapia CYP1B1 shows similarities of 79.7, 70.3, 65.7, 65.4, 65.0, and 63.7% with Plaice CYP1B1, Japanese eel CYP1B1, zebra fish CYP1B1, common carp CYP1B1, common carp CYP1B2 and  Channel catfish CYP1B1, respectively. The phylogenetic tree based on the amino acid sequences clearly shows tilapia CYP1B1  and Plaice CYP1B1 to be more closely related to each other than to the other CYP1B subfamilies. Furthermore, real-time PCR  was used for measuring BaP induction of CYP1B1 mRNA in different organs of tilapia (O. niloticus), using β-actin gene as internal control, and the results revealed that there was a large increase in CYP1B1 mRNA in liver (22.8), intestine (2.0) and muscles (1.3).Keywords: Oreochromis niloticus, benzo (a) pyrene, CYP1B1 cDNA, sequence analysis, real-time PCR

Effect of different additions on the crystallization behavior and magnetic properties of magnetic glass–ceramic in the system Fe2O3–ZnO–CaO–SiO2

AbstractThis work pointed out the preparation of a magnetic glass–ceramic in the system Fe2O3·ZnO·CaO·SiO2. The base composition was designed to crystallize about 60% magnetite. The influence of adding TiO2, Na2O and P2O5 separately or as mixtures was studied. The DTA of the glasses revealed a decrease in the thermal effects by adding P2O5, TiO2 and Na2O in an increasing order. The X-ray diffraction patterns showed the presence of nanometric magnetite crystals in a glassy matrix after cooling from the melting temperature. The crystallization of magnetite increased by adding TiO2, and P2O5, respectively, and decreased by adding Na2O. Heat treatment was carried out for the glasses in the temperature range of 1000–1050°C, for different time periods, and led to the appearance of hematite and β-wollastonite, which was slightly increased by adding P2O5 or TiO2 and greatly enhanced by adding Na2O. Samples containing mixtures of TiO2, Na2O, and P2O5 showed a summation of the effects of those oxides. The microstructure of the samples was examined by using TEM, which revealed a crystallite size of magnetite to be in the range of 52–90nm. Magnetic hysteresis cycles were analyzed using a vibrating sample magnetometer with a maximum applied field of 10kOe at room temperature in quasi-static conditions. From the obtained hysteresis loops, the saturation magnetization (Ms), remanence magnetization (Mr) and coercivity (Hc) were determined. The results showed that the prepared magnetic glass–ceramics are expected to be useful for a localized treatment of cancer

Comparative DNA profiling, botanical identification and biological evaluation of Gazania longiscapa DC and Gazania rigens L.

Gazania longiscapa DC and Gazania rigens L. are species of cultivated ornamental plant that grow in Egypt. Genus Gazania has a role in folk medicine to prevent toothache; this study presents a comparative investigation of genetic and botanical features of root, rhizome, leaves and flowers of the two Gazania species and comparing their biological activity as analgesic and antiinflammatory as related to their folk medicinal use. The genetic and botanical differences between the two Gazania species are reported for the first time in this study. The results contribute toward validation of the traditional use of Gazania showing that both species are safe for oral administration and they exhibit significant antinociceptive and anti-inflammatory effects in a dose dependent manner

Hepatoprotection and Antioxidant Activity of Gazania Longiscapa and G. Rigens with the Isolation and Quantitative Analysis of Bioactive Metabolites

Gazania longiscapa and G. rigens are two species belonging to family Asteraceae. The present study aimed the isolation of the main active constituents from the methanol extracts using different chromatographic methods and their identification using different spectroscopic techniques, beside the quantitation of some biologically important active constituent as rutin using HPLC technique, together with estimation of total polyphenolic content calculated as gallic acid and estimation of total flavonoid content calculated as rutin using UV technique. Concomitantly the determination of the antioxidant and hepatoprotective activity of the total methanol extracts of the aerial parts of G. longiscapa and G. rigens. This work resulted in the isolation of 4 flavonoids (Apigenin, Luteolin, Luteolin 7-O-β-D-glucopyranosid, Apigenin 7-O-β-Dglucopyranosid), 3 phenolic acids (Caffeic acid, Chlorogenic acid and 3,5- di- O-caffeoylquinic acid) from G. longiscapa for the first time; these 3 phenolic acids were also isolated from G. rigens, together with one flavonoid (rutin), The quantitative determination of the methanol extracts showed that G. longiscapa is a richer source of phenolic acids than G. rigens and both Gazania species are valuable sources of rutin beside having hepatoprotective and antioxidant activity

Safety evaluation of a bioglass–polylactic acid composite scaffold seeded with progenitor cells in a rat skull critical-size bone defect

Treating large bone defects represents a major challenge in traumatic and orthopedic surgery. Bone tissue engineering provides a promising therapeutic option to improve the local bone healing response. In the present study tissue biocompatibility, systemic toxicity and tumorigenicity of a newly developed composite material consisting of polylactic acid (PLA) and 20% or 40% bioglass (BG20 and BG40), respectively, were analyzed. These materials were seeded with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) and tested in a rat calvarial critical size defect model for 3 months and compared to a scaffold consisting only of PLA. Serum was analyzed for organ damage markers such as GOT and creatinine. Leukocyte count, temperature and free radical indicators were measured to determine the degree of systemic inflammation. Possible tumor occurrence was assessed macroscopically and histologically in slides of liver, kidney and spleen. Furthermore, the concentrations of serum malondialdehyde (MDA) and sodium oxide dismutase (SOD) were assessed as indicators of tumor progression. Qualitative tissue response towards the implants and new bone mass formation was histologically investigated. BG20 and BG40, with or without progenitor cells, did not cause organ damage, long-term systemic inflammatory reactions or tumor formation. BG20 and BG40 supported bone formation, which was further enhanced in the presence of EPCs and MSCs. This investigation reflects good biocompatibility of the biomaterials BG20 and BG40 and provides evidence that additionally seeding EPCs and MSCs onto the scaffold does not induce tumor formation

Characteristics of cells <i>in vitro</i> and evidence of cells seeded on the scaffold placed in the skull critical size defect.

<p>Shape and appearance of EPCs and MSCs obtained from rats in (A) and (B), respectively. Dil-uptake as a marker of endothelial differentiation is exemplarily shown for EPCs seeded on BG20 (C), the calcium deposition as measured by von Kossa staining revealed osteogenic differentiation of MSCs (black areas, D). Adherence of MSCs and EPCs one hour after seeding to the BG20 scaffold (E). MSCs and EPCs can be differentiated by size. Position of scaffold loaded with cells (arrow) in the skull critical size defect of the rat (F). Scale bars: 100 µm (A, B), 200 µm (D), 10 µm (E).</p

Surface characteristics and and biomechanical properties of disc shaped PLA, BG20 and BG40.

<p>Surface characteristics were analysed by SEM (A). The upper row provides an overview, the lower row presents a detailed view on distinct surface characteristics. Biomaterials with bioglass demonstrated a much more jagged surface with greater pores (arrows) than pure PLA. Red scale bar: 100 µm (upper row), 30 µm (Lower row). A sagittal cross section of PLA, BG20 and BG40 is shown in (B). PLA (left) appeared relatively homogenous with great cavities and pores, whereas BG20 (middle) and BG40 (right) demonstrated a biphasic structure. The upper part of BG20 and BG40 is characterized by an amorphic structure with pores and channels whereas the lower part has a higher density with few small pores. Red scale bar: 200 µm (PLA, BG20), 300 µm (BG40). The ultimate load of the disc shaped biomaterial specimen is depicted in (C). The median ultimate load as measured by a three point bending test increases slightly with the bioglass content of the biomaterials (n = 8, not significant).</p

Body weight (bw) and relative organ weight after 3 months.

<p>Results are presented as median (25%-quartile/75%-quartile). PLA = polylactic acid. BG20 = PLA + 20% bioglass, BG40 = PLA + 40% bioglass. EPC = endothelial progenitor cells, MSC = mesenchymal stem cells, dMSC = osteogenic predifferentiated MSC.</p

Group setup and number of animals per group.

<p>PLA = polylactic acid. BG20 = PLA + 20% bioglass, BG40 = PLA + 40% bioglass. MSC = mesenchymal stem cells, dMSC = osteogenic predifferentiated MSC, EPC = endothelial progenitor cells.</p