Green and one‐pot surface coating of iron oxide magnetic nanoparticles with natural amino acids and biocompatibility investigation

We report the synthesis of iron oxide magnetic nanoparticles (IONPs) coated with various natural amino acids (AAs) using a one‐pot reaction in an aqueous medium. Several AAs, which contained hydrophilic and hydrophobic groups, were selected to study their effects on size, morphology and toxicity of IONPs. Functionalized IONPs were characterized using X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and scanning and transmission electron microscopies. Furthermore, vibrating sample magnetometry analysis shows these nanoparticles have excellent magnetic properties. Cellular toxicity of IONPs was also investigated on HFF2 cell lines. The AA‐coated IONPs are non‐toxic and biocompatible. Natural AA‐coated IONPs show a potential for their development in in vitro and in vivo biomedical fields due to their non‐toxicity, good ζ‐potential and related small size and narrow size distribution.     

Preparation of bismuth sulfide nanoparticles as targeted biocompatible nano-radiosensitizer and carrier of methotrexate

In this study, Bi₂S₃@BSA–Bio–MTX nanoparticles (NPs) were synthesized for the first time by bovine serum albumin (BSA)-mediated biomineralization (Bi₂S₃@BSA NPs) followed by covalent bonding of biotin (Bio) and methotrexate (MTX) on the surface of the Bi₂S₃@BSA NPs via carbodiimide chemistry. The synthesized NPs were globular and exhibited uniform morphology with a hydrodynamic diameter of 107.6 ± 6.81 nm (mean ± standard deviation) and zeta potential of −20.9 ± 2.18 mV. Drug release from Bi₂S₃@BSA–Bio–MTX NPs indicated an enzyme-dependent release pattern. The in vitro biocompatibility of NPs was confirmed by investigating their cytotoxicity against the HEK-293 cell line and hemolysis assay test, whereas the in vivo biocompatibility of the NPs was evaluated and confirmed by the lethal dose 50 (LD₅₀) test. To evaluate the in vitro anticancer activity of the functionalized NPs and MTX, their cytotoxic effects was assessed against 4T1 cancer cells by 5-dimethylthiazol-z-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with and without X-ray radiation. Results showed that Bi₂S₃@BSA–Bio–MTX NPs have excellent anticancer activity, especially following X-ray radiation.     

Sono-chemical synthesis and characterization of Fe3O4@mTiO2-GO nanocarriers for dual-targeted colon drug delivery

Research on Chemical Intermediates - In this study, a kind of magnetic Fe3O4@mTiO2-GO (where m was shorted mesoporous) hybrids with core–shell nano-structure for controlled dual targeted drug...     

A Rapid and Sensitive LC–MS Method for Determination of Ezetimibe Concentration in Human Plasma: Application to a Bioequivalence Study

A selective and highly sensitive high performance liquid chromatography-electrospray ionization mass spectrometry method has been developed for determination of ezetimibe concentrations in human plasma. Ezetimibe was extracted from plasma with ethyl acetate followed by evaporation of the organic layer and, then, reconstitution of the residue in mobile phase before injection to chromatograph. The mobile phase consisted of acetonitrile-ammonium acetate (10 mM, pH 3.0), 75:25 (v/v). An aliquot of 10 μL was chromatographically analyzed on a prepacked Zorbax XDB-ODS C₁₈ column (2.1 × 100 mm, 3.5 micron). Detection of analytes was achieved by mass spectrometry with atmospheric pressure chemical ionization (APCI) interface in the negative ion mode operated under the multiple-reaction monitoring mode (m/z transition: ezetimibe 408–271). Standard curves were linear (r = 0.998) over the wide ezetimibe concentration range of 0.05–30.0 ng mL⁻¹ with acceptable accuracy and precision. The limit of detection was 0.02 ng mL⁻¹. The validated LC–APCI–MS method has been used successfully throughout a bioequivalence study on an ezetimibe generic product in 24 healthy male volunteers.

     

Synthesis and characterization of PEGylated iron and graphene oxide magnetic composite for curcumin delivery

Nowadays, nanostructures have been given significant attention in medical and biological fields. Among these nanostructures, graphene oxide (GO) has been widely used in drug delivery systems, because of its unique properties, and the ability to connect to other nanostructures such as magnetic nanoparticles (NPs) as well as polymers by its functional groups. In this research, first, GO was prepared by exfoliating graphite according to the modified Hummer’s method, and then the Fe₃O₄ NPs were synthesized by a simple co-precipitation method on GO nanosheets. In the next step, with the help of the ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide coupling reagents, the polyethylene glycol (PEG) polymer was bonded to the GO-Fe₃O₄ nanocomposite. Finally, anti-cancer drug, curcumin (Cur) was loaded onto the nanocomposite and the Cur loading ratio was measured at about 8%. The samples were evaluated using Fourier transform-infrared, differential scanning calorimtery, vibrating-sample magnetometry, atomic force microscopy and dynamic light scattering techniques. The results show that the prepared nanocomposite is an appropriate candidate for biomedical applications.     

Simple surface functionalization of magnetic nanoparticles with methotrexate-conjugated bovine serum albumin as a biocompatible drug delivery vehicle

Magnetic nanoparticles (MNPs) functionalized with methotrexate (MTX)-conjugated bovine serum albumin (BSA) as a biocompatible drug delivery vehicle were synthesized using a facile method. Characterization of the functionalized MNPs (Fe₃O₄@BSA-MTX NPs) was performed using various techniques including UV–visible spectroscopy, dynamic light scattering, vibrating sample magnetometry and X-ray diffraction. The particle size and zeta potential of Fe₃O₄@BSA-MTX NPs were 105.7 ± 3.81 nm (mean ± SD) and −18.2 mV, respectively. MTX release from Fe₃O₄@BSA-MTX NPs showed an enzyme-dependent release pattern. Hemo-biocompatibility of Fe₃O₄@BSA-MTX NPs was confirmed using hemolysis test. In addition, the cytotoxicity of functionalized MNPs and free MTX against MCF-7 cell line was investigated using MTT assay. The results of experiments revealed that the Fe₃O₄@BSA-MTX NPs as a biocompatible carrier could improve the therapeutic effect of MTX.     

Evaluation of UiO‐66 metal organic framework as an effective sorbent for Curcumin's overdose

Metal organic frameworks (MOFs) UiO‐66 (UiO stands for University of Oslo) and NH₂‐UiO‐66 were prepared and characterized as sorbent (antidotal agents) for curcumin (CUR) adsorption. The structure of products were characterized by X‐ray powder diffraction (XRD), Field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), Attenuated Total Reflectance‐Fourier transform infrared spectroscopy (ATR‐FTIR), and N₂ adsorption–desorption measurements. FESEM showed NH₂‐UiO‐66 displayed symmetrical crystals with triangular base pyramid morphology, with the particle size around 100 nm and uniform size distribution. Adsorption capacities of CUR/MOFs with different mass ratios in the feed were investigated in the present study, and this investigation revealed that when the CUR/MOFs with mass ratio was around 0.4, the absorption capacity of NH₂‐UiO‐66 had tended to maximum. Although, functionalization reduced the specific surface area and free volume, introducing polar amine groups could improve the affinity of NH₂‐UiO‐66 respect to CUR. Kinetic studies showed that the kinetic data are well fitted with the pseudo‐ second‐order model. MTT assay revealed that MOFs at the concentration range of 0–560 μg/ml had no cytotoxic effect on the Human Foreskin Fibroblast normal cell line (HFF‐2). These results suggest that these MOFs could be safe as sorbent for adsorb CUR from the body.     

A Rapid and Sensitive LC–MS Method for Determination of Ezetimibe Concentration in Human Plasma: Application to a Bioequivalence Study

A selective and highly sensitive high performance liquid chromatography-electrospray ionization mass spectrometry method has been developed for determination of ezetimibe concentrations in human plasma. Ezetimibe was extracted from plasma with ethyl acetate followed by evaporation of the organic layer and, then, reconstitution of the residue in mobile phase before injection to chromatograph. The mobile phase consisted of acetonitrile-ammonium acetate (10 mM, pH 3.0), 75:25 (v/v). An aliquot of 10 μL was chromatographically analyzed on a prepacked Zorbax XDB-ODS C₁₈ column (2.1 × 100 mm, 3.5 micron). Detection of analytes was achieved by mass spectrometry with atmospheric pressure chemical ionization (APCI) interface in the negative ion mode operated under the multiple-reaction monitoring mode (m/z transition: ezetimibe 408–271). Standard curves were linear (r = 0.998) over the wide ezetimibe concentration range of 0.05–30.0 ng mL^?1 with acceptable accuracy and precision. The limit of detection was 0.02 ng mL^?1. The validated LC–APCI–MS method has been used successfully throughout a bioequivalence study on an ezetimibe generic product in 24 healthy male volunteers.     

Bovine serum albumin stabilized iron oxide and gold bimetallic heterodimers: Synthesis,characterization and Stereological study

In this time researchers make a great efforts to develop new hybrid nanoparticles for medical and pharmaceutical applications. Fe₃O₄‐Au hybrid heterodimers have been prepared with superior properties for various claims. Unfortunately, Fe₃O₄‐Au heterodimers are not stable in the physiological medium. In this study, we employed the albumin macromolecules as a stabilizer of Fe₃O₄‐Au hybrid nanoparticles (noted as Fe₃O₄‐Au‐BSA hybrid nanoparticles). After characterization of synthesized nanoparticles by FTIR, UV–Vis, TEM, DLS, DSC, VSM and XRD techniques, the in vitro and in vivo biocompatibility of these nanoparticles were also evaluated. We encountered with an amazing result which confirmed nanoparticles could be stabilized by linking the BSA on the surface of Fe₃O₄‐Au heterodimers. Also, intravenous injection of Fe₃O₄‐Au‐BSA hybrid nanoparticles up to 400 mg/kg to Balb C mice show that these nanoparticles were non‐toxic. The biocompatibility and stereological study had been performed for more than 30 days after nanoparticles administration, using hystomorphometric analysis. Remarkably, to the best of our knowledge, it was the first time the biocompatibility and biodegradability of Fe₃O₄‐Au were studied and evaluated by stereological technique. Further promotion and biomedical usage of this type of hybrid nanoparticles are underway in our laboratory.