In spite of prosperous experiences in MS therapy, the future research, hopefully, will bring substantial improvements in the understanding and approaches of MS therapy.

The aim of this study was to evaluate the antibacterial effect of nisin-loaded chitosan/alginate nanoparticles as a novel antibacterial delivery vehicle. The nisin-loaded nanoparticles were prepared using colloidal dispersion of the chitosan/alginate polymers in the presence of nisin. After the preparation of the nisin-loaded nanoparticles, their physicochemical properties such as size, shape, and zeta potential of the formulations were studied using scanning electron microscope and nanosizer instruments, consecutively. FTIR and differential scanning calorimetery studies were performed to investigate polymer-polymer or polymer-protein interactions. Next, the release kinetics and entrapment efficiency of the nisin-loaded nanoparticles were examined to assess the application potential of these formulations as a candidate vector. For measuring the antibacterial activity of the nisin-loaded nanoparticles, agar diffusion and MIC methods were employed. The samples under investigation for total microbial counts were pasteurized and raw milks each of which contained the nisin-loaded nanoparticles and inoculated Staphylococcus aureus (ATCC 19117 at 10(6) CFU/mL), pasteurized and raw milks each included free nisin and S. aureus (10(6) CFU/mL), and pasteurized and raw milks each had S. aureus (10(6) CFU/mL) in as control. Total counts of S. aureus were measured after 24 and 48 h for the pasteurized milk samples and after the time intervals of 0, 6, 10, 14, 18, and 24 h for the raw milk samples, respectively. According to the results, entrapment efficiency of nisin inside of the nanoparticles was about 90-95%. The average size of the nanoparticles was 205 nm, and the average zeta potential of them was -47 mV. In agar diffusion assay, an antibacterial activity (inhibition zone diameter, at 450 IU/mL) about 2 times higher than that of free nisin was observed for the nisin-loaded nanoparticles. MIC of the nisin-loaded nanoparticles (0.5 mg/mL) was about four times less than that of free nisin (2 mg/mL). Evaluation of the kinetic of the growth of S. aureus based on the total counts in the raw and pasteurized milks revealed that the nisin-loaded nanoparticles were able to inhibit more effectively the growth of S. aureus than free nisin during longer incubation periods. In other words, the decrease in the population of S. aureus for free nisin and the nisin-loaded nanoparticles in pasteurized milk was the same after 24 h of incubation while lessening in the growth of S. aureus was more marked for the nisin-loaded nanoparticles than the samples containing only free nisin after 48 h of incubation. Although the same growth reduction profile in S. aureus was noticed for free nisin and the nisin-loaded nanoparticles in the raw milk up to 14 h of incubation, after this time the nisin-loaded nanoparticles showed higher growth inhibition than free nisin. Since, generally, naked nisin has greater interactions with the ingredients present in milk samples in comparison with the protected nisin. Therefore, it is concluded that the antibacteri...

Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer.

Conjugated Alpha-Alumina nanoparticle with vasoactive intestinal peptide as a Nano-drug in treatment of allergic asthma in mice, European Journal of Pharmacology, http://dx.doi.org/10.1016Pharmacology, http://dx.doi.org/10. /j.ejphar.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractAsthma is a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, airway hyperresponsiveness and recurring attacks of impaired breathing. Vasoactive intestinal peptide (VIP) has been proposed as a novel antiasthma drug due to its effects on airway smooth muscle relaxation, bronchodilation and vasodilation along with its immunomodulatory and anti-inflammatory properties. In the current study, we investigated the therapeutic effects of VIP when conjugated with α-alumina nanoparticle (α-AN) to prevent enzymatic degradation of VIP in the respiratory tract. VIP was conjugated with α-AN. Balb/c mice were sensitized and challenges with ovalbumin (OVA) or PBS and were divided in four groups; VIP-treated, α-AN-treated, α-AN-VIP-treated and beclomethasone-treated as a positive control group. Specific and total IgE level, airway hyperresponsiveness (AHR), bronchial cytokine expression and lung histology were measured. α-AN-VIP significantly reduced the number of 2 eosinophils (Eos), serum IgE level, Th2 cytokines and AHR. These effects of α-AN-VIP were more pronounced than that seen with beclomethasone or VIP alone (P<0.05). The current data indicate that α-AN-VIP can be considered as an effective nano-drug for the treatment of asthma.

nanoparticles modified with water soluble polymers for the diagnosis of breast cancer by MRI method, Journal of Magnetism and Magnetic Materials, http://dx.Abstract In this study, magnetic nanoparticles (MNPs) were synthesized via co-precipitation method. To enhance the biocompatibility and colloidal stability of the synthesized nanoparticles, they were modified with carboxyl functionalized PEG via dopamine (DPA) linker. Both modified and unmodified Fe 3 O 4 nanoparticles exhibited super paramagnetic behavior (particle size below 20nm). The saturation magnetization (Ms) of PEGdiacid-modified Fe 3 O 4 was 45 emu/g, which was less than the unmodified Fe 3 O 4 nanoparticles (70 emu/g). This difference indicated that PEGdiacid polymer was immobilized on the surface of Fe 3 O 4 nanoparticles successfully. To evaluate the efficiency of the resulting nanoparticles as contrast agents for magnetic resonance imaging (MRI), different concentration of MNPs and different value of echo time TE were investigated. The results showed that by increasing the concentration of the nanoparticles, transverse relaxation time (T 2 ) decreased, which subsequently resulted in MR signal enhancement. T2-weighted MR images of the different concentration of MNPs in different value of echo time TE indicated that MR signal intensity increased with increase in TE value up to 66 and then remained constant. The cytotoxicity effect of the modified and unmodified nanoparticles was evaluated in three different concentrations (12, 60 and 312 mgl -1 ) on MDA-MB-231 cancer cells for 24 and 48 h. In both tested time (24 and 48 h) for all three samples, the modified nanoparticles had long life time than unmodified nanoparticles. Cellular uptake of modified MNPs was 80% and reduced to 9% by the unmodified MNPs.

Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.

The use of dendrimers as nano-sized excipients/vectors in biological and pharmaceutical systems is dependent on the investigation of their toxicological profiles in biological media. In this study, a series of mechanistic in vitro structure-associated cell toxicity evaluations was performed on the two generations of an anionic linear-globular dendrimer G1 and G2 (where PEG is the core, and citric acid is the periphery) each of which has a different size, charge, and MW. In vitro cytotoxicity behavior of the dendrimers with the methods like crystal violet staining, methyl thiazolyl tetrazolium (MTT), and lactate dehydrogenase (LDH) assays was analyzed. The cell death mechanisms (apoptosis-necrosis) induced by the dendrimers were also evaluated in HT1080 cell line. The impact of the dendrimers on the release of the pro-inflammatory cytokines like TNF-alpha (tumor necrosis factor alpha) and IL1-beta (interleukin 1 beta) was assessed in THP-1 cell line. Hemolysis assay and coagulation studies such as PT (prothrombin time) and APTT (activated partial thromboplastin time) on human blood samples were conducted to examine the interactions of the dendrimers with such bio-environments. The results of cell cytotoxicity experiments and the amounts of IL1-beta and TNF-alpha secretions from THP-1 cell line were consistent with the hemoglobin release from the erythrocytes and the results gained from the coagulation studies. In fact, no significant harmful effect was observed for the dendrimers up to the concentration of 0.5 mg/ml. Both apoptosis and necrosis were ascribed to cell death. The G1 with more flexibility, less negative charge, and greater poly dispersity in size versus the G2 displayed more toxicity than the G2 at the concentration of 1 mg/ml and above in most of the experiments. As a whole, these results suggest a biocompatible range for these hybrid structures up to the concentration of 0.5 mg/ml. Therefore, the potentiality for these structures to be employed in the different and numerous realms of nanomedicine will be very great.

In the current study, in vitro biological feature of imatinib-loaded silver nanoparticles (IMAB-AgNPs) on human breast cancer cell line was investigated. The formation of synthesized silver nanoparticles (AgNPs) was characterized by UV-Visible spectroscopy, EDS, TEM imaging, SEM, FTIR, DLS and Zeta potentiometer. The developed IMAB-AgNPs with maximum percentage of loading efficiency was demonstrated in the average of 130 nm and mostly spherical. Additionally, in vitro drug release study showed a slow and continuous release of imatinib over a period of 80 h. We demonstrated that the synthesized IMAB-AgNPs exhibited a dose-dependent cytotoxicity against MCF-7 cell line. Then, real-time PCR method was also applied for the investigation of Bax and Bcl-2 gene expression in the cells. Comparing IMAB-AgNPs to AgNPs and Imatinib revealed the ability of IMAB-AgNPs to up-regulating Bax/Bcl-2 ratio. An induction of apoptosis was evidenced by Annexin-V/PI detection assay. Based on the current obtained data, the IMAB-AgNPs can exhibit inhibitory effect on viability through up regulation of apoptosis in MCF-7 cancer cells, which provides influencing evidence for the green synthesized AgNPs as a promising sustained drug delivery system.