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In this study, a novel method for intensification of drinking water production from seawater in a membrane distillation system is introduced. For this purpose, the feed water was passed through an intensive magnetic field and then introduced to the membrane module. The experiments were carried out for 80 h at different feed temperatures and flow rates, and different magnetic field intensities to ensure the effectiveness of the method. The best location for applying the magnetic field was determined, experimentally. In the absence of the magnetic field, a flux decline of about 50% was observed during 80 h of operation, while by applying three pairs of magnets, a 20% increase in the permeate flux and 72% decrease in the product TDS was observed. By increasing the magnetic field intensity, the size and the amount of the scale particles formed in the bulk solution increased but the analysis revealed that the scale build-up on the membrane surface was decreased upon applying the magnetic field. The process was optimized by the RSM method for obtaining the operating condition for attaining the best performance of the membrane system. At this optimum condition, an average permeate flux of 3.06 L/m2.h was obtained.

The UiO-66 NH2 and ZIF-8 metal organic framework nanoparticles (NMOFs) were incorporated into the polyvinylidene fluoride (PVDF) nanofibrous membrane. Then, the chitosan nanofibers were coated on the PVDF nanofibers to produce the PVDF/chitosan nanofibers. The performance of synthesized PVDF/NMOFs single layer and PVDF/chitosan/NMOFs two layers nanofibrous membranes was investigated for BSA protein molecules and Cr(VI) ions separation via ultrafiltration membrane process. The potential of synthesized nanofibers was also examined for BSA and Cr(VI) adsorption in a batch system. The characteristics of synthesized nanofibrous membranes were determined using SEM, EDX, TGA, BET, porosity and water contact angle measurements. The PVDF/chitosan nanofibrous membrane containing 20 wt% UiO-66-NH2, exhibited the maximum water flux of 470 L.m−2 h−1, 98.1% BSA rejection and 95.6% Cr(VI) rejection. The nanofibers were sucessfully regenrated for five adsorption-desorption cycles. The maximum sorption capacities of BSA and Cr(VI) were found to be 574.5 and 602.3 mgg−1, respectively. The obtained results revelaed the high potential of PVDF/chitosan/UiO66-NH2 nanofibers for membrane separation and adsorption of BSA molecules and Cr(VI) ions.

Since the discovery of RNAi and its therapeutic potential, carrier systems have been developed to deliver small RNAs (particularly siRNA) for modulation of gene expression at the post-transcriptional level. An important factor determining the fate and usability of these systems in vivo is interaction with blood components, blood cells, and the immune system. In this study, a lipid-based and a polymer-based carrier system containing siRNA have been investigated in vitro in terms of their hemocompatibility.The nanocomplexes studied were Angiplex, a targeted lipid-based system, and pHPMA-MPPM polyplex, a formulation based on a cationic polymer. siVEGFR-2 was encapsulated in both carriers and activation of platelets, coagulation, and complement cascade as well as induction of platelet aggregation were evaluated in vitro.Both systems had been shown before to cause significant silencing in vitro. Our findings indicated that pHPMA-MPPM polyplex triggered high platelet activation and aggregation although it did not stimulate coagulation substantially. Angiplex, on the other hand, provoked insignificant activation and aggregation of platelets and activated coagulation minimally. Complement system activation by Angiplex was in general low but stronger than pHPMA-MPPM polyplex.Taken together, these in vitro assays may help the selection of suitable carriers for systemic delivery of siRNA in early preclinical investigations and reduce the use of laboratory animals significantly.

Delivery of nucleic acids to tumors has received extensive attention in the past few decades since these molecules are capable of treating disease by modulating the source of abnormalities. Although high efficiency and low toxicity of numerous delivery systems for nucleic acids have been approved frequently with in vitro assays, contradictions have been observed in many cases between these results and what has occurred in the dynamic in vivo situation. Filling this gap seems to be crucial for further preclinical development of such systems. In this paper, we discuss various barriers which polymeric DNA or siRNA nanoparticles encounter upon systemic administration with an aim to assist in designing more relevant in vitro assays. Furthermore, individual considerations concerning delivery of DNA and siRNA have been addressed.

The adsorption of blood proteins onto liposomes and other colloidal particles is an important process influencing the circulation time. Proteins adsorbed to the surface of liposomes can mediate recognition of the liposomes by macrophages of the reticuloendothelial system (RES) facilitating their clearance from the circulation. Coating liposomes with poly(ethylene glycol) (PEG) decreases the blood clearance considerably, most likely due to reduced protein adsorption and/or liposome aggregation. By using the relation between clearance and protein binding, the present study introduces an in vitro assay measuring interactions of liposomes with proteins to predict their blood clearance in vivo. Such assay is valuable since it limits time and costs, and importantly reduces the number of animals required for pharmacokinetic investigations of new formulations. In the current study, Surface Plasmon Resonance (SPR) and fluorescence Single Particle Tracking (fSPT) were used to study liposome-protein interactions and blood induced liposome aggregation in vitro. By means of SPR the interactions between proteins and liposomes coated with PEG of different molecular weights and at different densities (PEG(2000) in 2.5%, 5% and 7%; PEG(5000) in 0.5%, 1.5% and 2.5%), were measured for several plasma proteins: human serum albumin (HSA), apolipoprotein E (ApoE), α2-macroglobulin (α2-M), β2-glycoprotein (β2-G) and fibronectin (Fn). Liposomes coated with PEG interacted less with all proteins, an effect which increased with the PEG surface density. In parallel, fSPT analysis showed that the exposure of liposomes to full blood did not change the liposome size, indicating that aggregation is not a strong attributive factor in the clearance of these liposomes. In addition, the SPR measurements of the interactions between liposomes and proteins were correlated with the blood clearance of the liposomes. For each protein, the degree of protein-liposome interaction as determined by SPR showed a moderate to strong positive correlation with the clearance of the liposome type.

Angiogenesis is one of the hallmarks of cancer which renders it an attractive target for therapy of malignancies. Tumor growth suppression can be achieved by inhibiting angiogenesis since it would deprive tumor cells of oxygen and vital nutrients. Activation of endothelial cells of tumor vasculature is the first step in angiogenesis which is mediated by various factors. One of the major triggers in this process is vascular endothelial growth factor (VEGF) which binds to VEGF receptors on endothelial cells of tumor vessels. This induces a series of signaling cascades leading to activation of cellular processes involved in angiogenesis, and therefore down-regulation of VEGF receptor-2 (VEGFR-2) expression seems a viable option to inhibit angiogenesis. In our investigations, this aim has been pursued by using siRNA interfering with the expression of VEGFR-2. Since the discovery of RNA interference (RNAi) as a gene regulation process, successful delivery of small non-coding RNA has presented itself as a major challenge. In the current study, we have characterized a galectin-1 targeted anginex-coupled lipoplex (Angiplex) containing siRNA against the gene of VEGFR-2 as an angiostatic therapeutic. Angiplex particles had a size of approximately 120 nm with a net negative charge and were stable in vitro. These particles were internalized in a specific manner by HUVECs compared to a non-targeted lipoplex system, and their uptake was higher than Lipofectamine 2000. Gene silencing efficiency of Angiplex was shown to be 61%.

In this study, the application of thermotropic liquid crystals embedded in cellulose nitrate membranes as on-off drug permeation control in response to temperature changes is described. Two low-molecular-weight liquid crystals, n-pentyl-cyanobiphenyl (K15) and n-heptyl-cyanobiphenyl (K21), with nematic-to-isotropic phase transition temperatures (T(n-i)) of 36.3 °C and 43.3 °C, respectively, were used to modulate drug permeation through the membrane. Liquid crystal-embedded membranes composed of appropriate blends of K15 and K21 were prepared by vacuum filtration. The permeation of pyrazinamide and metronidazole as drug models with different hydrophilicity and molecular weights through the liquid crystal-embedded membrane was examined. It was found that the drug permeation through the membrane could be modulated by changing the temperature below and above the T(n-i) of liquid crystals. The permeation of pyrazinamide, the hydrophilic drug with smaller molecular weight, was more temperature-dependent than metronidazole, the hydrophobic drug with higher molecular weight. These experiments were also repeated with thermal cycling between 25 °C and 45 °C. The permeation profiles were reversible and followed zero-order kinetics.

An improved pegylated liposomal formulation of docetaxel has been developed with the purpose of improving the docetaxel solubility without any need to use tween80 that is responsible for hypersensitivities following administration. Liposomes all had spherical shape with size of 130–160 nm. The most important finding of this study is that pegylated liposomes were prepared with significant increase in docetaxel encapsulation efficiency and stability of the formulation in comparison with last reports on docetaxel liposomes. In vitro release studies revealed that such a formulation could be stable in the blood circulation and meet the requirements for an effective drug delivery system.

Tumor-angiogenesis is the multi-factorial process of sprouting of endothelial cells (EC) into micro-vessels to provide tumor cells with nutrients and oxygen. To explore miRNAs as therapeutic angiogenesis-inhibitors, we performed a functional screen to identify miRNAs that are able to decrease EC viability. We identified miRNA-7 (miR-7) as a potent negative regulator of angiogenesis. Introduction of miR-7 in EC resulted in strongly reduced cell viability, tube formation, sprouting and migration. Application of miR-7 in the chick chorioallantoic membrane assay led to a profound reduction of vascularization, similar to anti-angiogenic drug sunitinib. Local administration of miR-7 in an in vivo murine neuroblastoma tumor model significantly inhibited angiogenesis and tumor growth. Finally, systemic administration of miR-7 using a novel integrin-targeted biodegradable polymeric nanoparticles that targets both EC and tumor cells, strongly reduced angiogenesis and tumor proliferation in mice with human glioblastoma xenografts. Transcriptome analysis of miR-7 transfected EC in combination with in silico target prediction resulted in the identification of OGT as novel target gene of miR-7. Our study provides a comprehensive validation of miR-7 as novel anti-angiogenic therapeutic miRNA that can be systemically delivered to both EC and tumor cells and offers promise for miR-7 as novel anti-tumor therapeutic.