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Endothelial vasomotor dysfunction and accelerated atherosclerosis encompass the features of rheumatoid vascular dysfunction (RVD), increasing cardiovascular morbidity and mortality among rheumatoid arthritis (RA) patients. Methotrexate, among DMARDs, effectively reduces cardiovascular events, but its non-selectivity together with its pharmacokinetic variability often limit drug adherence and contribute to its potential toxicity. Thus, methotrexate was conjugated to gold nanoparticles (MTX/AuNPs) and its effect on RVD in rats’ adjuvant-induced arthritis was evaluated. A comparative study between MTX/AuNPs, free MTX, and AuNPs treatments on joint inflammation, vascular reactivity and architecture, smooth muscle phenotype, systemic inflammation, and atherogenic profile was done. Since MTX/AuNPs effect was superior, it appears that conjugation of MTX to AuNPs demonstrated a synergistic action. MTX immunomodulatory action combined with AuNPs anti-atherogenic potential yielded prompt control of whole features of RVD. These findings highlight the usefulness of nanoparticles-targeted drug-delivery system in refining rheumatoid-induced vascular dysfunction treatment and reviving gold use in RA.

The present study investigated the anti-Toxoplasma effect of chitosan nanoparticles [CS NPs], spiramycin, spiramycin co-administered with metronidazole and spiramycin-CS NPs formulation on the parasite burden and histopathological changes in the liver, spleen and brain in experimentally infected mice. Seventy male Swiss albino mice were classified into seven equal groups: healthy control (I), infected untreated control (II), infected group receiving CS NPs (III), spiramycin administered infected group (IV), infected group receiving spiramycin-metronidazole (V), infected receiving 400 mg/kg spiramycin-CS NPs (VI) and infected treated with spiramycin-loaded CS NPs 100 mg/kg (VII). All groups were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain except the healthy control group. All groups were sacrificed on the 8th day after infection. Density of the parasite and histopathological examination of the liver, spleen and brain of all treated mice revealed reduction in the mean tachyzoites count as well as decreased inflammation, congestion and necrosis within tissue sections. Spiramycin-loaded NPs displayed the highest significant reduction in the pathological insult tailed by spiramycin-metronidazole and CS NPs. In conclusion, spiramycin-loaded CS NPs showed a promising synergistic combination in the treatment of the histopathology caused by toxoplasmosis.

In this study, curcumin nanoemulsion (CR-NE) was used in the preparation of processed cheese as a functional and healthy ingredient. Curcumin nanoemulsion showed higher antibacterial activity against Staphylococcus aureus, Clostridium sporogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas marginalis strains. Curcumin nanoemulsion was added to processed cheese formula by ratio 2.5% and 5% (T1 and T2) to reach a final concentration of 25 mg and 50 mg of nanocurcumin/kg processed cheese, respectively, and physicochemical, textural, microstructure, and organoleptic properties were tested. The results showed that the addition of CR-NE improved the physicochemical, microstructure, and textural properties of processed cheese during cold storage at 4°C for 60 days. Curcumin nanoemulsion decreased the loss of moisture during storage. The hardness of cheese containing CR-NE was slightly changed during storage compared with control samples. The T1 samples recorded the best sensory evaluation scores compared with T2 samples. No significant differences were found in acceptability between T1 samples and control samples during storage. The T1 processed cheese samples obtained represent high quality and healthy product that adds value to the dairy sector.

Localized hyperthermia is a very promising cancer therapy approach especially when stimulated by the exceptional properties of iron oxide magnetic nanoparticles (MNPs). This approach is a highly site-specific method for localized heating of bodily tissue without any harmful side effects that could revolutionize the practice of cancer therapy. The main objective of this study was to evaluate the cancer cell-destroying capability of MNPs in combination with ultrasound treatment as an innovative sonomagnetic cancer therapy. Magnetic nanofluids (MNFs) were synthesized by co-precipitation/sonochemical techniques in an aqueous medium without any surfactant and/or capping agent. The physicochemical characteristics of the prepared MNFs were investigated with scanning electron microscopy, transmission electron microscopy, X-ray diffractometry, Fourier transform infrared and vibrating sample magnetometry. The MNFs was used as a mediator and sonosensitizer to destroy tumor tissue when irradiated by ultrasound waves. The antitumor efficiency of MNFs in combination with pulsed ultrasound (1.5 W/cm2, 1 MHz) was evaluated in vitro and in vivo. In vitro efficacy was estimated by determining the cell viability of Ehrlich ascites carcinoma cells. For in vivo experiments, female mice were inoculated subcutaneously with Ehrlich carcinoma cells to establish solid Ehrlich carcinoma. The cytotoxic concentration of MNFs (400 µg/mL) was injected intratumorally and exposed to pulsed ultrasound (1.5 W/cm2, 1 MHz). The cytotoxic effect was determined in terms of tumor growth rate, apoptosis and necrosis. Our results revealed that MNFs in the presence of pulsed ultrasound cause a significant increase in the cytotoxicity effect on tumor cells. This study illustrates the high efficiency of cancer therapy as assisted by both ultrasound and magnetic nanofluid.

Introduction Type 1 diabetes mellitus is an autoimmune disorder characterized by inflammatory damage to pancreatic β cells resulting in loss of insulin secretion. In autoimmune type 1 diabetes mellitus (T1D) natural killer cells (NK) initiate pancreatic islets cell lyses in autoimmune T1D. Loss of T regulatory cells (Treg) at disease onset facilitates the activation and accumulation of NKs in the pancreatic microenvironment. A proper low-dose interleukin 2 (IL-2) could enhance Tregs and enforce control and regulation of pro-inflammatory NKs. Aim This relation needs to be studied to improve therapeutic strategies aimed at resetting the balance between Tregs and proinflammatory cells. Material and methods We used novel formulations of low-dose IL-2 loaded on chitosan nanoparticles. The study included 116 T1D BALB/c mice experimentally induced by streptozotocin, divided into groups. Their splenocytes were maintained in a short-term culture for assessment of expression of CD4+FOXP3+ Treg and NKp46+NK by both flow cytometry and enzyme-linked immunoassay (ELISA). Morphological, immunohistochemical, and morphometrical analyses were done. In vitro suppressor assay was used to assess the suppressor effect of Treg cells after exogenous IL-2 treatment. Results NK cell expression, NKp46 level, and NK cell functions were modulated more in mice injected with IL-2-loaded chitosan nanoparticles than in other groups. A statistical inverse correlation was found between Treg and NK cell expression in IL-2-loaded chitosan with 0.3 µIU (p = 0.047), and this correlation was related to FOXP3 expression on Treg cells. The modified expression of NK and NKp46 was noticed in mice injected with 0.3 µIU for longer duration (3 weeks) (p < 0.001), but the NK functions did not show any significant changes with prolonged treatment. Conclusions Prolonged administration of low-dose IL-2 results in the vigorous expression of NKp46, indicating a significant role of Tregs in NK stimulation and motivation. Low-dose IL-2 selectively modulates NKp46 NK and FOXP3+ Tregs and increases their expression.

This work aimed to intensively study polypropylene samples (PP) embedded with micro- and nanoparticles of Bi2O3 for their application in radiation shielding. Samples were prepared by adding 10%, 20%, 30%, 40%, and 50% of Bi2O3 microparticles (mBi2O3) by weight, and adding 10% and 50% of Bi2O3 nanoparticles (nBi2O3), in addition to the control sample (pure polypropylene). The morphology of the prepared samples was tested, and also, the shielding efficiency of gamma rays was tested for different sources with different energies. The experimental LAC were determined using a NaI scintillation detector, the experimental results were compared with NIST-XCOM results, and a good agreement was noticed. The LAC values have been used to calculate some specific parameters, such as half value layer (HVL), mean free path (MFP), tenth value layer (TVL), and radiation protection efficiency (RPE), which are useful for discussing the shielding capabilities of gamma rays. The results of the shielding parameters show that the PP embedded with nBi2O3 gives better attenuation than its counterpart, PP embedded with mBi2O3, at all studied energies.

Background and Objective: Although the anticancer potentials of water-insoluble drugs are improved by nanoformulation, other intervening factors may contribute in the drug efficacy. This work was designated to explore the effect of paclitaxel-loaded Poly(Lactic-co-Glycolic Acid) (PLGA) nanoparticles on the viability of cancer cells, the expression of Taxol Resistance gene I (TXR1) and paclitaxel metabolizing genes. Methods: Paclitaxel loaded PLGA Nanoparticles (PTX-NPs) were prepared, physically characterized and used in the treatment of breast adenocarcinoma cells (MCF-7) and hepatoma cells (HepG2). Cells viability and apoptosis were investigated. In parallel, RNA was isolated, reverse transcribed and used to monitor the expression levels of TXR1, CYP 3A4 and CYP2C8 genes. Results: PTX-NPs were characterized by transmission electron microscopy to be of a nano-size sphere-like shape. FTIR analysis revealed good coupling between PTX and PLGA. The encapsulation efficiency was 99% and the drug release demonstrated a progressive releasing phase followed by slower and sustained releasing phases. Although HepG2 cells demonstrated more resistance to PTX than MCF-7 cells, both cell types were more responsive to PTX-NPS compared to PTX. The IC50 values decreased from 19.3 to 6.7 in breast cancer cells and from 42.5 to 13.1μg/ml in hepatoma cells. The apoptosis was the key mechanism in both cells, where at least 44% of cells underwent apoptosis. The expression of TXR1 decreased when either cells were treated with PTX-NPs, respectively, meanwhile the expressions of CYP3A4 and CYP2C8 were increased. Conclusion: Taken together, this in vitro study reports the associations between the enhanced responsiveness of MCF-7 and HepG2 cells to PLGA-loaded paclitaxel nanoparticles and the accompanying decrease in the cells resistance to the PTX and its enhanced metabolism.

Doxorubicin (DOX) effectiveness in cancer treatment is hampered by its nonspecific accumulation in organs. Ultrasound (US) is a promising noninvasive targeting approach. Currently, studies focus on developing more DOX-loaded US-triggered formulations with different composition, DOX doses, and US intensities. No studies were emerged to compare and select the most effective approach to endure. The aim of this study is to prepare and comparatively address the therapeutic potential of 2 different US-tunable nanosized liposomes while minimizing DOX dose and US intensity. One of the liposomes is tailored to be responsive for US non-thermal effects (DOX-USLs) and the other is designed to be thermoresponsive (DOX-TSLs). Both systems were compared in terms of cellular uptake, cell viability and apoptosis using HeLa cells as a cancer model. The IC50 of DOX-USLs and DOX-TSLs was 2.5–5 times lower than that of free DOX. IC50 reflected the significant superior cytotoxicity of DOX-TSLs (0.1 μg/mL) over DOX-USLs (0.2 μg/mL). Cellular uptake indicated that DOX-TSLs were inside the nucleus while DOX-USLs were accumulated everywhere in the intracellular space with lower fluorescent intensity inside the nucleus. However, both showed enhanced apoptosis in terms of enhanced caspase-3 activity, reduced glutathione levels and DNA fragmentation when compared to free DOX treatment.

Due to the negative impact of the heavy metal ions in water, the rejection of these toxic materials is one of the urgent requests for wastewater treatment. This work aims to facile fabrication and characterization of new organic/inorganic hybrid nanofiber membrane composites for removal of Fe (III) and Pb (II) ions using a batch technique. The manufacturing of pure cellulose acetate nanofibers (CA NFs) and its impregnated with hydroxyapatite (CA/HAp) nanocomposite fibers is explored by an electrospinning process. A production process of uniform and bead-free nanofiber is developed by adjusting various electrospinning conditions. The experiments prove that the slight changes in operating parameters may result in significant variations in the fiber morphology. The influence of various adsorption conditions and its effect on the removal efficiency is investigated. High separation efficiency of about 99.7 and 95.46% within 35 and 40 min. for adsorption Pb (II) and Fe (III) ions using hybrid nanofiber composite, respectively are obtained. The adsorption process was found to obey a pseudo-second-order and Freundlich models. The adsorption mechanism on the CA/HAp composite can be established via ion exchange and surface complexation.

Recently, polymers have entered into many medical and industrial applications. This work aimed to intensively study polypropylene samples (PP) embedded with micro and nanoparticles of PbO for their application in radiation shielding. Samples were prepared by adding 10%, 30%, and 50% by weight of PbO microparticles (mPbO) and adding 10% and 50% PbO nanoparticles (nPbO), in addition to the control sample (pure polypropylene). The morphology of the prepared samples was tested; on the other hand, the shielding efficiency of gamma rays was tested for different sources with different energies. The experimental linear attenuation coefficient (LAC) was determined using a NaI scintillation detector, the experimental results were compared with NIST-XCOM results, and a good agreement was noticed. The LAC was 0.8005 cm−1 for PP-10%nPbO and 0.6283 cm−1 for PP-10%mPbO while was 5.8793 cm−1 for PP-50%nPbO and 3.9268 cm−1 for PP-50%mPbO at 0.060 MeV. The LAC values have been converted to some specific values, such as half value layer (HVL), mean free path (MFP), tenth value layer (TVL), and radiation protection efficiency (RPE) which are useful for discussing the shielding capabilities for gamma-rays. The results of shielding parameters reveal that the PP embedded with nPbO gives better attenuation than its counterpart pp embedded with mPbO at all studied energies.

Healing of injuries caused by exposure to heat has been discussed in many studies, although a few drugs have been shown to produce satisfactory results. In this study, 100 healthy mice randomly allocated into four categories (each = 25 mice) were analyzed. A deep second-degree burn on the back of each mouse was created. The burns were dressed daily with either AgNPs or silver sulfadiazine over 28 days of treatment. Safety evaluation of the AgNP treatment was performed by measuring the deposition rate of silver in the liver, brain, and kidney of treated mice. In the murine burn model, the speed of wound healing and the antibacterial effect of AgNPs were better than those in the silver sulfadiazine group. Burn wounds treated with SSD appeared to display a greater degree of inflammation as notable by the three clinical signs of the inflammatory process such as redness and swelling which appeared to be less after wounds treated with AgNPs. Also, AgNP treatment modified leukocytic infiltration and reduced collagen degeneration in treated mice and enhanced healing processes that were confirmed by morphological and histological investigations. Beside the potential significant effects of AgNPs on reduction of some microorganism counts that routinely isolated from burn wounds included aerobic organisms as Staphylococcus aureus and Escherichia coli when compared to both SSD and control groups. The deposition kinetics of AgNPs revealed lower distribution in the liver, brain, and kidney than that in silver sulfadiazine-treated mice with respect to both SSD and control groups.

Praziquantel (PZQ) is the main treatment of Schistosomiasis mansoni. However, resistance to it was described. So, there is a necessity to develop novel drugs or to enhance the present drugs. This work aimed to assess the efficacy of PZQ alone and when loaded on liposomes in treatment of S. mansoni infection by parasitological and histopathological studies in experimental murine models. 112 male laboratories bred Swiss Albino mice were used in this work. They were divided into four groups: Group 1: control group; Group 2: infected then treated by PZQ (500 mg/kg) at 7, 30 and 45 days post infection; Group 3: infected then treated by liposome encapsulated PZQ (lip.PZQ) (500 mg/kg) at 7, 30 and 45 days post infection; Group 4: infected then treated by free liposomes at 7, 30 and 45 days post infection. The results showed that G3 caused the highest significant reduction of the total worm count, eggs/gram liver tissue and intestine (97.2%, 99.3%, 99.5%) respectively. Followed by G2 (85.1%, 97.6%, 89.8%) respectively. Regarding the histopathological studies, G3 showed the highest significant reduction in number and diameter of hepatic granuloma (97.6% and 98.1%), followed by G2 (77.2% and 75%) when compared to other groups. In conclusion, lip.PZQ is more effective than free PZQ from all aspects especially when administered 45 days PI.

Thesis Abstract Background: Breast cancer is a heterogeneous disease that mandate efficient therapeutics, lower drug toxicity, and overcoming drug resistance. Combination therapy was suggested as a future treatment to attain the required efficacy and tolerable side effects. Aim: The current study aimed to compare and evaluate the efficacy of single and combined treatments in the MCF-7 breast cancer cell line. Materials and Methods: The study included seven MCF-7 groups according to the treatment modality. Cell viability was evaluated by MTT assay at different doses and time course treatments. Results: When nanoparticles were used alone, the starting point of significant cell death was 100 µg, but when using a photothermal combination modality the loss of viability % was bout 2- fold higher than nanoparticles alone especially in low concentrations and there was a significant difference between the 2 groups. There was a significant difference in cell viability between FAC + AuNPs group when compared to FAC only or control group (p ≤ 0.05). There was a significant difference in cell viability between Taxol + AuNPs when compared to control (p ≤ 0.05). there is a significant effect of radiation doses on cell viability within all subgroups ( p < 0.001 for R0, and p=0.001 for R2 subgroup). there is a significant effect of the radiation doses on the cell viability within each subgroup as indicated by significant p values ( p= 0.027 for RN0, and p=0.001 for RN2). Conclusion: Combined GNPs and FAC, paclitaxel, and Radiotherapy treatment modalities could improve breast cancer outcomes and prognosis.

The present study investigated the anti-Toxoplasma effect of chitosan nanoparticles [CS NPs], spiramycin, spiramycin co-administered with metronidazole and spiramycin-CS NPs formulation on the parasite burden and histopathological changes in the liver, spleen and brain in experimentally infected mice. Seventy male Swiss albino mice were classified into seven equal groups: healthy control (I), infected untreated control (II), infected group receiving CS NPs (III), spiramycin administered infected group (IV), infected group receiving spiramycin-metronidazole (V), infected receiving 400 mg/kg spiramycin-CS NPs (VI) and infected treated with spiramycin-loaded CS NPs 100 mg/kg (VII). All groups were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain except the healthy control group. All groups were sacrificed on the 8th day after infection. Density of the parasite and histopathological examination of the liver, spleen and brain of all treated mice revealed reduction in the mean tachyzoites count as well as decreased inflammation, congestion and necrosis within tissue sections. Spiramycin-loaded NPs displayed the highest significant reduction in the pathological insult tailed by spiramycin-metronidazole and CS NPs. In conclusion, spiramycin-loaded CS NPs showed a promising synergistic combination in the treatment of the histopathology caused by toxoplasmosis.

Silver nanoparticles (AgNPs) are being used extensively for biomedical purposes regarding to their broad antimicrobial activity, however their toxicity has been addressed in only few studies. In the present study, we aimed to prepare and characterize AgNPs, investigate their adverse effect on liver and kidney functions, and also elucidate the hepato-nephro protective ability of tannic acid in male rats. The obtained results showed that AgNPs caused oxidative stress throughout the induction of thiobarbituric acid-reactive substances (TBARS) and the reduction of the activities of antioxidant enzymes (GST, SOD, CAT, GPx) and the levels of glutathione. Hepatic markers enzymes (AST, ALT, ALP, ACP, LDH and GGT), total bilirubin, urea, creatinine and lipid profile were increased, while hematological parameters were decreased. Histopathological investigations indicated marked degeneration of hepatocytes, endothelial cells of renal which with its role has confirmed the hepatotoxicity and nephrotoxicity induced by AgNPs. The presence of tannic acid along with AgNPs showed obvious improvements in the injured liver and kidney tissues. The protective effect of tannic acid against the toxicity of AgNPs might be due to its antioxidant properties and scavenging abilities against active free radicals.

Gemcitabine was loaded in albumin nanoparticles then coated with chitosan. The diameter of GEM-ANPs/CS was 200 ± 4 nm. Gemcitabine was loaded in GEM-ANPs/CS with an efficacy of 75%. The IC50 of GEM...

Constituting the host-parasite interface and playing a censorious role in host immune response modulation and parasite survival, tegument represents a crucial target for many antischistosomal drugs. Sphingomyelin forms a stable outer leaflet of tegumental membrane-lipid bilayer. Neutral magnesium‏-dependent sphingomyelinase (Mg2+-nSMase) is a key enzyme in sphingomyelin breakdown was identified in schistosomes. We investigated the in vivo efficacy of ubiquinol, a natural inhibitor of Mg2+-nSMase, in free and niosomes-encapsulated forms, through five-day and 15-day regimens on the early and late Schistosoma mansoni parasitic stages, respectively, compared to PZQ. Oral administration of 300mg/kg/day ubiquinol-encapsulated niosomes (U-N) showed significant deterioration of the parasitic growth and development in the term of reduction of lung schistosomula burden (39.12 %), adult worm burden (50.81 %), hepatic and intestinal tissue-egg counts (80.89 % and 75.54 %, respectively). PZQ and free ubiquinol regimens reported reductions in lung schistosomula counts (45.36% and 22.90%, respectively) and total worm burdens of 86.28 % and 24.58 %, respectively. U-N therapy revealed worms de-pairing and remarkable diminution in female worms’ perimeters and fecundity. Scanning electron microscope revealed disruption of tegumental ridges with excessive longitudinal corrugation. Transmission electron microscope showed testicular and ovarian parenchymal degeneration, signs of immaturity and cell apoptosis. Indirect immunofluorescence assay approved parasite's tegumental changes. Remarkable reduction of granulomas size with amelioration of hepatic pathology and fibrosis were assumed to be attributed to the anti-inflammatory and anti-oxidant properties of ubiquinol. These findings with the drug safety profile suggest that U-N could be a promising candidate for a new antischistosomal drug development.

Safety of drinking-water is an urgent for human health. It is critical to promote the cheap technologies for water purification to guarantee the free-pathogens-drinking water. The present study has been investigated the antibacterial activity of polyacrylonitrile (PAN) nanofibers membranes which decorated by Ag, CuO or ZnO nanoparticles as bactericides. The hybrid nanofiber composites were fabricated by electrospinning technique and the obtained membranes were characterized using SEM, EDX and FTIR. Their antibacterial activity was evaluated against E. coli and S. aureus. The data was revealed that the functionalization was successfully obtained by the incorporation of nanoparticles as an additive into the polymer solution which associated many superior properties. Continuous PAN membrane fibers with average diameters from 170 to 250 nm without any beads of plain and its hybrid membrane composites were obtained. The antimicrobial activity was estimated using both disk diffusion tests and growth kinetic models. The antibacterial activity was improved as the concentrations of nanoparticles enhanced. This study provided the real solution for production and inactivation of bacteria which related to the impregnated the PAN nanofibers membrane with Ag, CuO or ZnO NPs. The results have significant implications for finding a safe and an inexpensive path to solve the problems of drinking water, especially in the developing countries.

So far, liver fibrosis still has no clinically-approved treatment. The loss of stored vitamin-A (VA) in hepatic stellate cells (HSCs), the main regulators to hepatic fibrosis, can be applied as a mechanism for their targeting. Valsartan is a good candidate for this approach; it is a marketed oral-therapy with inverse- and partial-agonistic activity to the over-expressed angiotensin-II type1 receptor (AT1R) and depleted nuclear peroxisome proliferator-activated receptor-gamma (PPAR-γ), respectively, in activated HSCs. However, efficacy on AT1R and PPAR-γ necessitates high drug permeability which is lacking in valsartan. In the current study, liposomes were used as nanocarriers for valsartan to improve its permeability and hence efficacy. They were coupled to VA and characterized for HSCs-targeting. Tracing of orally-administered fluorescently-labeled VA-coupled liposomes in normal rats and their fluorescence intensity quantification in different organs convincingly demonstrated their intestinal entrapment. On the other hands, their administration to rats with induced fibrosis revealed preferential hepatic, and less intestinal, accumulation which lasted up to six days. This indicated their uptake by intestinal stellate cells that acted as a depot for their release over time. Confocal microscopical examination of immunofluorescently-stained HSCs in liver sections, with considerable formula accumulation, confirmed HSCs-targeting and nuclear uptake. Consequently, VA-coupled valsartan-loaded liposomes (VLC)-therapy resulted in profound re-expression of hepatic Mas-receptor and PPAR-γ, potent reduction of fibrogenic mediators' level and nearly normal liver function tests. Therefore, VLC epitomizes a promising antifibrotic therapy with exceptional extended action and additional PPAR-γ agonistic activity.

Oral administration of insulin is hampered by the lack of carriers that can efficiently achieve high encapsulation, avoid gastric degradation, overcome mucosal barriers, and prolong the hypoglycemic effect. Chitosan (CS)-coated insulin-loaded cationic liposomes have been developed and optimized for improved oral delivery. Liposomes were prepared cationic to improve insulin encapsulation. CS was selected as a mucoadhesive coat to prolong the system's residence and absorption. The performance of CS-coated liposomes compared with uncoated liposomes was examined in vitro, ex vivo, and in vivo in streptozotocin-induced diabetic mice. Free uncoated liposomes showed high positive zeta potential of +58.8 ± 2.2 mV that reduced (+29.9 ± 1.4 mV) after insulin encapsulation, confirming the obtained high entrapment efficiency of 87.5 ± 0.6%. CS-coated liposomes showed nanosize of 439.0 ± 12.3 nm and zeta potential of +60.5 ± 1.9 mV. In vitro insulin release was limited to 18.9 ± 0.35% in simulated gastric fluid, whereas in simulated intestinal fluid, 73.33 ± 0.68% was released after 48 h from CS-coated liposomes. Ex vivo intestinal mucoadhesion showed increased tissue residence of CS-coated liposomes compared with uncoated liposomes. A striking reduction in the glucose level was observed 1 h after oral administration of CS-coated liposomes and maintained up to 8 h (p0.01 vs. insulin solution or uncoated liposomes) within the normal value 129.29 ± 3.15 mg/dL. In conclusion, CS-coated insulin-loaded cationic liposomes improved loading efficiency with promising prolonged pharmacological effect.

Efficacy of alginate nanoparticles (Alg-NPs) as vaccine delivery for the excretory-secretory antigens (ESAs) against the virulent strain of Toxoplasma gondii was evaluated. Swiss albino mice were intraperitoneally immunized with three doses of either in vivo and in vitro-prepared ESA vaccines, 20 µg each, at 2-week intervals, then were challenged with 2500 tachyzoites of the RH HXGPRT (-) Toxoplasma gondii strain, four weeks later. Mice mortality, tachyzoite number in both peritoneal fluid and impression smear, and viability, ultrastructural tachyzoite changes, measuring immunological markers, and histopathological changes of both liver and spleen were studied, in comparison to alum adjuvanted ESAs and infected control subgroups. The in vivo-prepared Alg-NPs loaded ESAs vaccinated subgroups induced significant reduction in mice mortality, tachyzoite count in both peritoneal fluid and impression smears and viability. Scanning electron microscopy revealed tachyzoites deformities with multiple irregularities, while transmission electron microscopy showed tachyzoites distortion, disrupted plasma membranes, loss of nuclear integrities, and absence of dense granules with extensive vacuolations. A statistically significant increase in the level of both IFN-γ and anti-Toxoplasma IgG was noted. Histopathological results recorded amelioration of the pathological changes induced by Toxoplasma infection in both liver and spleen, with scanty parasites. Therefore, Alg-NPs proved its effectiveness in enhancing the ESAs antigencity, and recommended to test its potentiality as drugs carrier for anti-Toxoplasma agents to enhance their therapeutic efficacy.

A marked reduction has been achieved in the incidence and clinical course of toxoplasmic encephalitis after the introduction of protease inhibitors within the treatment regimen of HIV (HIV-PIs). This work was undertaken to study for the first time, the efficacy of HIV-PIs, lopinavir/ritonavir (L/R), as a therapeutic agent in acute experimental toxoplasmosis. Lopinavir/ritonavir (L/R) were used in the same ratio present in aluvia, a known HIV-PIs drug used in the developing countries in the treatment regimens of AID's patient. Poly lactic-co-glycolic acid (PLGA) nanoparticles were used as a delivery system to L/R therapy. L/R alone or after its encapsulation on PLGA were given to Swiss strain albino mice that were infected with RH virulent toxoplasma strain. Both forms caused parasitological improvement in both mortality rate and parasite count. The higher efficacy was achieved by using L/R PLGA together with minimizing the effective dose. There was significant reduction in the parasite count in the peritoneal fluid and the liver. Parasite viability and infectivity were also significantly reduced. The anti-toxoplasma effect of the drug was attributed to the morphological distortion of the tachyzoites as evident by the ultrastructure examination and suppressed the egress of tachyzoites. L/R also induced changes that suggest apoptosis and autophagy of tachyzoites. The parasitophorous vacuole membrane was disrupted and vesiculated. The nanotubular networks inside the parasitophorous vacuole were disrupted. Therefore, the present work opens a new possible way for the approved HIV-PIs as an alternative treatment against acute toxoplasmosis. Furthermore, it increases the list of the opportunistic parasites that can be treated by this drug. The successful in vivo effect of HIV-PIs against Toxoplasma gondii suggests that this parasite may be a target in HIV treated patients, thus decrease the possibility of toxoplasmic encephalitis development.

Spiramycin-metronidazole and spiramycin-loaded chitosan (CS) nanoparticles (NPs) were tested in comparison with the current spiramycin treatment of T.gondii concerning tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain and were divided into experimental and control groups. The experimental groups orally received CS NPs, spiramycin, spiramycin-metronidazole, spiramycin-loaded CS NPs 400 mg/kg and spiramycin-loaded CS NPs 100 mg/kg. Drug efficacy was assessed by mice survival time, mortality rate, parasite load in different organs and morphological study of the tachyzoites movement by light microscope and the ultra-structure by SEM. The results revealed that the maximum survival time of more than 200 days with no mortality on the sacrifice day (8th) was observed in mice receiving spiramycin-loaded NPs. Spiramycin-loaded NPs showed the highest significant percent reduction of tachyzoites (about 90% reduction) in liver, spleen and brain as compared to the other used drugs denoting successful bypass of BBB. Light microscopy of the treated peritoneal tachyzoites showed sluggish tachyzoites movement while the NPs caused loss of their movement. SEM of the treated tachyzoites were more mutilated and some of them appeared rupturing in those receiving CS NPs and spiramycin-loaded NPs. In conclusion, spiramycin-loaded NPs showed the highest efficiency in the treatment of acute toxoplasmosis. The non-toxic nature and the anti-parasitic effect of both CS and spiramycin make the use of spiramycin-loaded CS NPs a potential material for treatment of human toxoplasmosis.

Introduction Natural killer cells (NK) initiate pancreatic islets cell lyses in autoimmune type 1 diabetes mellitus (T1D). Loss of T regulatory cells (Treg) at disease onset facilitates activation and accumulation of NKs in the pancreatic microenvironment. A proper low dose interleukin 2 (IL-2) could enhance Tregs and enforce control and regulation of pro-inflammatory NKs. This relation needs to be studied to improve therapeutic strategies aimed at resetting the balance between Tregs and proinflammatory cells. Material and methods We used novel formulations of low dose IL-2 loaded on chitosan nanoparticles. The study included 116 T1D BALB/c mice experimentally induced by streptozotocin, divided into groups. Their splenocytes were maintained in a short-term culture for assessment of expression of CD4+Foxp3+ Treg and NKp46+NK by both flow cytometry and enzyme linked immunoassay (ELISA). In vitro suppressor-assay was used in order to assess the suppressor effect of Treg cells after exogenous IL-2 treatment. Results NK cell expression, NKp46 level and NK cell functions were modulated in mice injected with IL-2 loaded chitosan nanoparticles than other groups. A statistical inverse correlation was found between Treg and NK cell expression in IL-2 loaded chitosan with (0.3 µIU) (p = 0.047) and this correlation was related to Foxp3 expression on Treg cells. The modified expression of NK and NKp46 was noticed in mice injected with (0.3 µIU) for longer duration (three weeks) (p < 0.001) but the NK functions did not show any significant changes with prolonged treatment. Conclusions Low dose (0.3) µIU IL-2 nanoparticles effectively modulated NK and NKp46 expression. It selectively modulates the suppressive activity of Tregs indicating a significant role of Tregs in NK activation and function by controlling the availability of IL-2 in the microenvironment.

Novel magnetic cellulose acetate (CA) nanofibers were fabricated using an electrospinning process. Co-precipitated magnetite iron oxide nanoparticles were immobilized onto CA nanofibers at different weight ratios (0.2–2.5% wt/v) with a CA concentration of 15% (wt %), applied electric voltage of 20 kV, feeding rate of 1.5 ml/h and 7 cm distance between needle tip and collector. The prepared iron oxide nanoparticles were characterized using X-ray diffraction, a transmission electron microscope, a Fourier transform infrared spectrophotometer (FT-IR) and a vibrating sample magnetometer (VSM). The magnetic nanofibers were characterized by scanning electron microscopy, FT-IR, thermogravimetric analysis and VSM. The fabricated composite nanofibers were evaluated as a sorbent matrix for lead decontamination from aqueous solution using a batch technique. The influence of solution pH, contact time and adsorbent concentration on the removal efficiency was investigated. Adsorption kinetics models and isotherms were applied to the lead decontamination process onto the fabricated composite nanofibers. The kinetics of the sorption process revealed that the pseudo-second-order model fitted relatively better than the pseudo-first-order model. On the other hand, both the Langmuir and Freundlich isotherms gave a comparable fit to the adsorption data, with a high coefficient of regression of 0.999.

Although the chemosensitizing effect of Dexamethasone (DEX) and its ability to increase the sensitivity of breast cancer cells to chemotherapy were previously reported, this study aimed to explore how far cotreatment of breast cancer cells with paclitaxel (PTX) and DEX mimics the anticancer effect of nanoformulated PTX. To establish this goal, PTX was nanoformulated with poly (lactic-co-glycolic acid) (PLGA) and the nanoparticles (PTX-NPs) were physically authenticated. Breast cancer cells (MCF-7) were treated with PTX or PTX-NPs in presence or absence of low concentration (10 nM) of DEX. Cells viability (assessed by MTT assay), apoptosis (assessed by flow cytometry) and the expression of PTX resistance gene (TRX1) and PTX metabolizing genes (CYP2C8 and CYP3A4) were investigated. The results showed that nanoformulated PTX was validated by nano-size assessment, increased the anionic surface charge and prober conjugation with the biodegradable carrier (PLGA), as indicated by the FTIR spectroscopy. Initially, the IC50 value of PTX was 19.3 μg/ml and cotreatment with DEX minimized it to 5.22 μg/ml, whereas PTX-NPs alone inhibited cell proliferation with IC50 6.67 μg/ml. Also, in presence of DEX, PTX-NPs further decreased the IC50 to 5 μg/ml. In parallel, DEX has increased the responsiveness of cells to PTX without potentiating its apoptotic effect. Moreover, the glucocorticoid (with PTX or PTX-NPs) downregulated TXR1 gene by 26% (P

Water shortage is among the critical challenges facing many countries located in the arid zone of the southern the Mediterranean region. In the northern Sinai, El-Salam Canal and shallow groundwater in the Quaternary aquifer are considered the main irrigation sources for reclamation of 62,000 acres situated along the Mediterranean coast. The chemistry of surface water of El-Salam Canal varies greatly from the western to the eastern sides. Additionally, the groundwater chemistry is greatly influenced by dilution due to seepage of El-Salam Canal water. The historical and recent records of water chemistry show great variation of the concentrations of dissolved Al3+, Cu2+ and Zn2+ in both surface and groundwater, based on sampling time and locality. The concentrations of these heavy metals occasionally exceed the international recommended limits for drinking and short-term irrigation standards. The removal of dissolved heavy metals from water is crucial to fill the gap between the water supply and the growing demands using possible techniques of water treatment. Consequently, zeolite nanocomposites are one of the materials that have been used for water treatment. Magnetic zeolite nanocomposites (MZNCs) were prepared by the chemical co-precipitation of Fe2+ and Fe3+ in the presence of zeolite. The prepared magnetic nanocomposites were characterized by TEM, SEM, EDX, XRD, FTIR, TGA and VSM. The results show that MZNCs have a cubic crystal structure and good thermal stability. The MZNCs were used to remove Al(III), Zn(II) and Cu(II) from simulated water and then were easily separated from the medium by external permanent magnet. Batch adsorption experiments were conducted, and the effects of pH, initial ion concentration, adsorbent dose and contact time were studied. The selected pH range (pH = 5–6) and temperature (27 °C) in the batch adsorption experiments were close to the pH range of the surface and groundwater field data. Furthermore, the chosen initial concentrations and adsorbent doses were within the heavy metals concentration ranges in El-Salam Canal and the adjacent groundwater. The MZNCs show great removal capacity of heavy metals where 0.1 g is able to clean contaminated water with high concentrations (0.5–3 g/l) of Cu(II) and Zn(II) within 20 min and within 30 min for Al(III). The adsorption kinetics data of the system were well fitted to pseudo-second-order model, which indicates a faster kinetic sorption by the composites. Adsorption isotherms were studied using Langmuir and Freundlich isotherms. Although both of them fit the data, the Freundlich isotherm had the best fit for the selected metals.

Physical treatments such as therapeutic ultrasound and Laser are cited as important aides in wound management. This work expected to assess the role of ultrasound and laser on excisional wound healing progression in incited diabetic mice. Forty Swiss albino mice were divided into 2 groups; group I (diabetic free, 10mice) was used as a control group, while the other; group II(30 mice) was diabetic induced. Circular wounds were created on the dorsal fur of the animals. The wounds of laser treated group (N=10) were exposed to laser irradiation (830nm, 60mW), 5 minutes daily, 5 days/week until the wounds healed completely. The wounds of ultrasound treated group (N=10) were exposed to pulsed ultrasound (0.5 W/cm2 , 1MHz) 5 minutes daily until the wounds healed completely. The untreated group (N=10) wound was left without treatment. The wounds for control group did not receive any type of treatment. The healing was noticed and assessed during the treatment period. Histological analysis of mice skin was accomplished at days 4, 10 and 15 post- wounding. Taking after healing period and determine the mechanical properties of healed skin. By looking at results acquired from various treatment modalities, we found that the two remedial devices encourage and quicken diabetic injury recuperating and enhancing scar quality yet with various degrees. Lighted injury with laser exhibited a more propelled recuperating process than ultrasound treated gathering. We can conclude that, both low-power laser and ultrasound treatments may quicken cutaneous injury mending in diabetic injury model. This finding may widen current treatment regimens

Toxoplasmosis, a zoonotic parasitic disease, is a huge challenge for which there is no effective vaccine up till now. In this study, chitosan nanospheres encapsulated with Toxoplasma lysate vaccine was evaluated for its ability to protect mice against both acute and chronic toxoplasmosis models of infection. Results showed that chitosan nanospheres were equally effective to Freund's incomplete adjuvant (FIA) in enhancing the efficacy of Toxoplasma lysate vaccine. The effectiveness was demonstrated by the delayed death of vaccinated mice following challenge either with virulent RH or avirulent Me49 strains, the significant decrease in parasite density in different organs, significant increase in the humoral and cellular immune response (IgG and IFN γ) with a marked reduction of pathological changes in the different organs. However chitosan nanospheres were superior to FIA due to their cost effective preparation and much less necrotic changes induced in the studied organs. The success of chitosan polymer as an alternative to commonly used adjuvants paves the way for the use of other newly developed polymers to be used in the field of vaccine development.

BackgroundGold nanoparticles (GNPs) are currently used in several consumer products as well as in laboratory-based research either as a diagnostic imaging agent or as a therapeutic agent in gene delivery and photothermal cancer therapy. They are synthesized by chemical methods in which toxic reducin

With the increased prevalence of antibiotic-resistant bacteria infections, there is a pressed need for innovative antimicrobial agent. Metal nanoparticle, especially those made of noble metals such as silver, show excellent properties such as signaling the regeneration of collagen, low toxicity in vivo, bacteriostatic and bactericidal activities, and inhibiting the targeting of bacteria in wound. Therefore, this study aims to prepare silver nanoparticles then investigate its antimicrobial effect in wound healing in animal model. Silver nanoparticles were successfully prepared by chemical reduction of silver nitrate, then characterized by UV-Visible absorption spectroscopy. The in-vivo study was done by application of colloidal solution of silver nanoparticles on excisional full- thickness skin defect on the dorsum of New Zeeland rabbit as an animal model. The results indicated significant reduction of the sepsis in two infected cases after the 1st week followed by complete recovery after the 2nd dose of (SNPs drops). While the other cases showed wound closure without any sepsis which demonstrated the high efficiency of silver nanoparticles as antimicrobial agent when compared with the control group which showed persistent signs of sepsis in the all cases. The histological investigation in the control group proved that the quality of the healing process was very poor. The lengths of the newly formed epithelium, collagen deposition, and the granulation thickness are considered the positive signs of the wound healing process which obviously observed with the animal treated with SNPs.it could be concluded that silver nanoparticles can be used as an effective antimicrobial agent as promising step instead of using systemic the antibiotics.

Impaired wound healing is a common complication of diabetes mellitus. Nanofibre can be served as powerful tools in advanced wound care management. The aim of this work is to evaluate the role of antibacterial nanofibres by incorporating silver nanoparticles into celluose acetate nanofibres as wound dressing on excisional wound healing in diabetic mice. Celluose acetate nanofibres were prepared by electrospinning technique. The prepared nanofibres were characterised using scanning electron microscope (SEM), and Fourier-transform infrared (FTIR) spectrophotometer. The antimicrobial activity was tested against Gram-positive and Gram-negative bacteria. A full thickness of the excision wound of circular area 95 mm2 and 2 mm depth was created. Wound dressed by silver containing nanofibres, the wound closure rate were assessed, skin wounds were processed for histopathological examination and comparing the mechanical properties of healed skin. It was found that, wounds dressed with silver containing nanofibres showed marked increase in collagen production which improve the skin mechanical properties.

Anti-microbial nanofibers can be synthesized by incorporating nanobiocides such as silver nanoparticles into nanofibers. Bacterial contamination of water is a serious public health concern because it causes numerous diseases and some aesthetic problems such as malodor in water. Durable antibacterial Ag/polyacrylonitrile (Ag/PAN) hybrid nanofibers were prepared by electrospinning. SEM and EDX spectra were used to study the morphology and surface elemental composition of the nanofibers. The Ag/PAN nanofibers exhibited slow and long lasting silver ion release. The resultants polymers were then tested for their ability to destroy bacteria in water; antimicrobial tests indicated that the prepared nanofibers have a high bactericidal effect. Accordingly, these results highlight the potential use of these nanofibrous mats as antimicrobial agents.