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Zoledronic acid (ZA) is known as a potent bisphosphonate in osteogenic differentiation, but at high doses, it possesses toxic effects and causes decreased proliferation and differentiation of osteoblasts. Therefore, encapsulation of ZA into nanoparticles and control of its release is expected to promote differentiation of stem cells into osteoblasts. The present work aimed to develop a simple method for synthesis of monodisperse ZA-loaded chitosan (CS) nanoparticles. In this regard, we proposed a microfluidic synthesis of nanoparticles through the ionic cross-linking of CS in the presence of ZA without a crosslinker. The main advantages of these microfluidic generated nanoparticles were narrow size distribution and fine spherical shape. Conversely, the nanoparticles that were synthesized using a bulk mixing method had an irregular shape with a broad size distribution. Real-time PCR assay as well as alizarin red staining were used to evaluate the in-vitro osteogenic potential of the nanoparticles. The results indicated that the controlled release of ZA from the microfluidic system generated uniform nanoparticles, improving the osteogenic differentiation of mesenchymal stem cells. Additionally, this microfluidic device provided the well-controlled synthesis of novel nanoparticles with a modified CS macromolecular polymer for targeted drug delivery systems.

A novel series of benzylpyridinium-based benzoheterocycles (benzimidazole, benzoxazole or benzothiazole) were designed as potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The title compounds 4a-q were conveniently synthesized via condensation reaction of 1,2-phenylenediamine, 2-aminophenol or 2-aminothiophenol with pyridin-4-carbalehyde, followed by N-benzylation using various benzyl halides. The results of in vitro biological assays revealed that most of them, especially 4c and 4g, had potent anticholinesterase activity comparable or more potent than reference drug, donepezil. The kinetic study demonstrated that the representative compound 4c inhibits AChE in competitive manner. According to the ligand-enzyme docking simulation, compound 4c occupied the active site at the vicinity of catalytic triad. The compounds 4c and 4g were found to be inhibitors of Aβ self-aggregation as well as AChE-induced Aβ aggregation. Meanwhile, these compounds could significantly protect PC12 cells against H2O2-induced injury and showed no toxicity against HepG2 cells. As multi-targeted structures, compounds 4c and 4g could be considered as promising candidate for further lead developments to treat Alzheimer's disease.

In the present study, the anticancer drug temozolomide (TMZ) was initially loaded into the chitosan (CS) nanoparticles and synthesized CS/TMZ nanoparticles were incorporated into the synthesized poly (ε-caprolactone diol) based polyurethane (PCL-Diol-b-PU) nanofibers. The synthesized nanoparticles and nanofibers were characterized using dynamic light scattering, transmission electron microscopy, X-ray powder diffraction and scanning electron microscopy. The obtained results revealed that the CS/TMZ nanoparticles were successfully embedded into the PCL-Diol-b-PU nanofibers. The gold nanoparticles with average particle size of 18nm were synthesized and coated on the nanofibers surface to enhance the antitumor activity of CS/TMZ loaded nanofibers against inhibiting the growth of U-87 MG human glioblastoma cells. The sustained TMZ release for 30days with the zero order kinetic model were achieved from both CS/TMZ loaded PCL-Diol-b-PU and gold-coated nanofibers. The cell viability results indicated that the gold-coated nanofibers can effectively inhibit the growth of U-87 glioblastoma cells. Therefore, the prepared gold-coated CS/TMZ loaded PCL-Diol-b-PU nanofibers would be a potential candidate for glioblastoma cancer treatment.

The coupling of adsorption and photo-Fenton processes has been studied for the simultaneous removal of phenol and paracetamol from aqueous systems. Photo-Fenton process exhibited the complete elimination of phenol and paracetamol during 1 h. For mineralization of contact time, the adsorption process was combined to the photo-Fenton process. The both NaX nanozeolites and cobalt ferrite nanoparticles were synthesized by microwave heating method and were used through the adsorption and photo-Fenton processes, respectively. The nanoparticles were characterized by XRD and SEM analysis. The Box–Behnken design was applied to evaluate the effect of key parameters including pH (3–4), phenol initial concentration (20–100 mg L−1), paracetamol initial concentration (20–100 mg L−1) and NaX to cobalt ferrite nanoparticles ratio (0.5–1.5) on the simultaneous removal of phenol and paracetamol at contact time of 30 min. By optimization of parameters, the removal percentages of phenol and paracetamol were found to be 99.95% and 99.80%, respectively. The results demonstrate that the coupling of adsorption and photo-Fenton processes is an alternative method to eliminate the phenolic compounds from wastewaters.

In the present study, the photo-Fenton process was applied for the treatment of phenol and paracetamol in a binary system. The cobalt ferrite nanoparticles synthesized by microwave heating method were applied during photo-Fenton process. The nanoparticles were characterized by XRD and SEM analysis. The response surface methodology based on Box–Behnken design was used to evaluate and optimize the interactive effects of five operating variables including pH, initial concentrations of phenol and paracetamol, H 2 O 2 concentration and cobalt nanoferrite dosage on the phenol and paracetamol degradation rates in photo-Fenton process. The results of experimental design indicated that the pH of 3.5, H 2 O 2 concentration of 50 mmol/L and cobalt nanoferrite dosage of 0.2 g/L maximize the efficiency of phenol and paracetamol degradation rates at the time in photo-Fenton process. The maximum experimental phenol and paracetamol degradation efficiencies for initial concentrations of 20 mg/L of phenol and paracetamol were found to be 95 and 85%, respectively. These values were in good agreement with the estimated values by the model in optimum conditions (94.5 and 84.4% for phenol and paracetamol degradation efficiencies). The obtained results demonstrated an excellent ability of synthesized cobalt ferrite nanoparticles to remove the phenolic compounds in photo-Fenton process.

In the present study, adsorption and photo-Fenton processes have been compared for the removal of phenol and paracetamol from aqueous solutions in a single and binary systems. NaX nanozeolites and cobalt ferrite nanoparticles were used during adsorption and photo-Fenton processes, respectively. Both nanoparticles were synthesized using microwave heating method. The synthesized nanoparticles were characterized using powder X-ray diffraction (XRD) and scanning electronic microscopy (SEM) analysis. Based on results, more than 99% removing percentages of phenol and paracetamol were obtained during photo-Fenton process at initial concentrations of 10, 20, 50, 100 and 200 mg/L of phenol and paracetamol. Moreover, the complete removing of phenol and paracetamol was only achieved at lower initial concentrations than 10 mg/L for phenol and paracetamol during adsorption process. The results showed a significant dependence of the phenol and paracetamol removing on the initial concentrations of phenol and paracetamol for selection of process. The photo-Fenton process could be considered an alternative method in higher initial concentrations of phenol and paracetamol. However, the adsorption process due to economical issue was preferred for phenol and paracetamol removing at lower initial concentrations. The kinetic data of photo-Fenton and adsorption processes were well described using first-order and pseudo-second-order kinetic models. The results of phenol and paracetamol removing in a binary system confirmed the obtained results of single removing of phenol and paracetamol in selection of process.

Objective To to compare the chitosan/alginate, chitosan and alginate nanoparticles as plasmid vectors, to determine the morphological characteristics, size and physicochemical properties of nanoparticle-pEGFP complexes and to evaluate the potential of these nanoparticles in transfection of pEGFP plasmid in to a cultured the human embryonic kidney cell line (HEK 293 cells). Methods Nanoparticles comprising chitosan, alginate and both chitosan-alginate polymers were formed through pregel preparation method. The ability of plasmid-complexes in preventing DNA migration were assessed by the agarose gel assay. The efficiency of nanoparticles in transfection of pEGFP plasmid in the cultured HEK 293 cells was measured by flow cytometry. The effect of the nanoparticle-plasmid complexes on the cell viability was determined using cytotoxicity assay. Resutls Chitosan, alginate and alginate/chitosan nanoparticles had a mean Z-average diameter of 620 nm, 235.8 nm and 161.8 nm and mean zeta potential of 45 mV, −18.6 mV and 29.3 mV, respectively. Chitosan and chitosan/alginate nanoparticles have greater capacity to maintain plasmid than alginate nanoparticles. Alginate nanoparticles had the greater transfection in comparison to the others. Cell viability assays indicated that nanoparticles had no toxic effect on HEK 293 cells after 4 h or 24 h. Conclusions The combination of particle surface, hydrophobicity size and zeta potential can influence on transfection efficiency and the cellular uptake of the nanoparticles. Our suitable candidate for gene delivery would be alginate/chitosan nanoparticles.

Chitosan/alginate nanoparticles optimized for size and loading efficiency were evaluated for their potential of antisense oligonucleotide delivery. The antisense for epidermal growth factor receptor (EGFR) that is over-expressed in many cancer cells was loaded in chitosan/alginate nanoparticles. The T47D breast cancer cell line was chosen to study the efficiency of optimized nanoparticles (chitosan/alginate 1:1, alginate/calcium chloride 0.2% and N/P ratio of 5 and 25) on EGFR expression. The MTT cytotoxicity evaluation of nanoparticles confirmed non-toxic properties of these carriers. The FITC-labeled EGFR antisense showed that T47D cells can uptake antisense-loaded nanoparticles better than naked antisense. Both RT-PCR and immunocytochemistry analyses showed that nanoparticles with N/P ratio of 5 can downregulate the expression of EGFR in T47D breast cancer cell line by improving internalization and stability of antisense molecules.

Nanoparticles comprising Alginate/Chitosan polymers were prepared by pregel preparation method through drop wise addition of various concentrations of CaCl2 to a defined concentration of Sodium Algi- nate. Then, Chitosan/Antisense solution with a certain N/P ratio was added to the pregel to make the nanoparticles. The effect of such parameters as polymer ratio, CaCl2/Alginate ratio and N/P ratio on the particle size distribution and loading efficacy was studied. The optimum conditions were 1:1 (w/w) Algi- nate to Chitosan ratio, 0.2% CaCl2/Alginate ratio and N/P ratio of 5 at pH 5.3. The resulting nanoparticles had a loading efficacy of 95.6% and average size of 194 nm as confirmed by PCS method and SEM images showed spherical and smooth particles. The zeta potential of optimized nanoparticles prepared by this method was about +30 mV which could result in good stability of nanoparticles during manipulation and storage.

The mechanical properties of elongated tablets of different thickness prepared at a range of pressures with surfaces that are flat or curved, have been determined by application of a flexure test. The strength of the tablets in terms of breaking load increases with an increase in the cross-sectional area of the tablets. To provide an improved method of comparing the strength of the tablets, the tensile strength of the specimens has been calculated from equations based on stress analysis. While an allowance for a change in thickness was provided by such a system there was a clear indication that the specimens tensile strength was still dependent on their dimensions. For equivalent central core thickness strength increased with the face curvature. This could be due to changes of the structure within the specimen during the formation process and there were clear indications that tablet porosities for equivalent compaction pressures were not equal. The differences could, however, be utilised to provide optimum conditions of curvature and central core thickness to give maximum tablet strength.