Doxorubicin-loaded cholic acid-polyethyleneimine micelles for targeted delivery of antitumor drugs: synthesis,characterization, and evaluation of their in vitro cytotoxicity

Doxorubicin-loaded micelles were prepared from a copolymer comprising cholic acid (CA) and polyethyleneimine (PEI) for the delivery of antitumor drugs. The CA-PEI copolymer was synthesized via pairing mediated by N,N’-dicyclohexylcarbodiimide and N-hydroxysuccinimide using dichloromethane as a solvent. Fourier transform infrared and nuclear magnetic resonance analyses were performed to verify the formation of an amide linkage between CA and PEI and doxorubicin localization into the copolymer. Dynamic light scattering and transmission electron microscopy studies revealed that the copolymer could self-assemble into micelles with a spherical morphology and an average diameter of <200 nm. The CA-PEI copolymer was also characterized by X-ray diffraction and differential scanning calorimetry. Doxorubicin-loaded micelles were prepared by dialysis method. A drug release study showed reduced drug release with escalating drug content. In a cytotoxicity assay using human colorectal adenocarcinoma (DLD-1) cells, the doxorubicin-loaded CA-PEI micelles exhibited better antitumor activity than that shown by doxorubicin. This is the first study on CA-PEI micelles as doxorubicin carriers, and this study demonstrated that they are promising candidates as carriers for sustained targeted antitumor drug delivery system.     

Highly efficient supported AlCl3-based cationic catalysts to produce polyα-olefin oil base stocks

The main aim of this research is to decrease the amount of AlCl₃ content that is very corrosive and hazardous in the catalytic system, required for the α-olefin oligomerization without substantial change of final oil features. This was successfully achieved by supporting AlCl₃ on different carriers. More precisely, a series of supported bimetallic catalysts was synthesized by immobilization of AlCl₃ and TiCl₄ onto Al₂O₃, SiO₂, and mixed supports, that is, Al₂O₃/FeCl₃ and SiO₂/FeCl₃. It was found that silica and alumina-based catalysts had higher catalytic activities compared to support free AlCl₃; however, this enhancement for silica-based supports was more significant. According to gel permeation chromatography (GPC) results, the use of single supports, that is, Al₂O₃ and SiO₂, increased oligomer's molecular weight, while the application of mixed supports resulted in the decrease of molecular weight of the oligomers. Viscosity characteristics of the synthesized oligomers have also been studied at two different temperatures of 40 and 100°C (KV⁴⁰ and KV¹⁰⁰). The viscosity index (VI) values, derived from KV⁴⁰ and KV¹⁰⁰, of the prepared oligomers were in the range of 126–145. The molecular weight and termination mechanisms of the oligomers were studied by ¹H-NMR spectroscopy. The obtained results disclosed that the employed reaction conditions led to the production of oligomer chains with various structures including vinylidene (Vd), and di and three-substituted vinylene (2Vn, 3Vn) structures.     

Optimization of a continuous ultrasound assisted oxidative desulfurization (UAOD) process of diesel using response surface methodology (RSM) considering operating cost

A continuous-flow ultrasound-assisted oxidative desulfurization(UAOD) of partially hydro-treated diesel has been investigated using hydrogen peroxide-formic acid as simple and easy to apply oxidation system. The effects of different operating parameters of oxidation stage including residence time(2–24 min), formic acid to sulfur molar ratio(10–150), and oxidant to sulfur molar ratio(5–35) on the sulfur removal have been studied using response surface methodology(RSM) based on Box–Behnken design. Considering the operating costs of the continuous-flow oxidation stage including chemical and electrical energy consumption, the appropriate values of operating parameters were selected as follows: residence time of 16 min, the formic acid to sulfur molar ratio of 54.47, and the oxidant to sulfur molar ratio of 8.24. In these conditions, the sulfur removal and the volume ratio of the hydrocarbon phase to the aqueous phase were 86.90% and 4.34, respectively. By drastic reduction in the chemical consumption in the oxidation stage, the volume ratio of the hydrocarbon phase to the aqueous phase was increased up to 10. Therefore, the formic acid to sulfur molar ratio and the oxidant to sulfur molar ratio were obtained 23.64 and 3.58, respectively, which lead to sulfur removal of 84.38% with considerable improvements on the operating cost of oxidation stage in comparison with the previous works.     

Polymer lifetime studies in hostile environments

Photo-oxidative degradation reactions are mainly responsible for reduced lifetime in polymers. These reactions are responsible for the decay in useful physical and chemical properties of polymers. In addition to high ultraviolet radiation doses, hostile environments have increased temperature, high humidity, and air-borne sand. In this work white pigmented polyvinyl chloride (PVC) pipe sections were exposed to natural weather at seven different locations. Characterization studies were made on exposed samples using Fourier transform infrared (FTIR) spectroscopic, gel permeation chromatographic (GPC), and scanning electron microscopic (SEM) studies. Performance characteristics were determined by testing changes in the mechanical properties. Functional groups introduced during the processing of PVC and irregularities in the polymer chain can be held responsible for the initiation and propagation of photo-oxidative degradation reactions catalyzed by high surface temperature and increased humidity.     

Determination of 4-nonylphenol and 4-tert-octylphenol compounds in various types of wastewater and their removal rates in different treatment processes in nine wastewater treatment plants of Iran

Alkylphenols(APs), considered as xenoestrogenic compounds, mainly exist as 4-nonylphenol(4-NP) and 4-tertoctylphenol(4-t-OP) in environments. The high stability and accumulation of APs in aquatic systems have caused endocrine disruption. In this study we measured APs in the wastewater influent and effluent samples, from the urban, rural, livestock, commercial and hospital wastewater treatment plants(WWTPs) in Iran. Dispersive liquid–liquid microextraction(DLLME) combined with gas chromatography–mass spectrometry(GC–MS) was used for the extraction and determination of 4-NP and 4-t-OP. In these treatment plants, various processes such as activated sludge, aerated lagoon, moving bed biofilm reactor and activated sludge along with wetland were applied. The highest concentration of 4-NP and 4-t-OP was observed in commercial and livestock sewages. The activated sludge along with wetland and then the MBBR process showed the highest removal rates of pollutants. The rates of biodegradability and accumulation in sludge were determined and also the specific adsorption coefficient Kdand the organic carbon–water partition coefficient kOCof the sludge for APs were calculated.     

Synthesis,characterization, rheological and thermal behavior of metallocene ethylene − norbornene copolymers with low norbornene content using pentafluorophenol modified methylaluminoxane

Ethylene ? norbornene copolymers were synthesized using rac‐ethylene bis(indenyl) zirconium dichloride/pentafluorophenol modified methylaluminoxane. First, the effect of using a modifier in combination with a low ratio of Al/Zr on the catalyst activity and co‐monomer incorporation was studied. The results of copolymerization reveal a 20% co‐monomer incorporation improvement and a rise of activity by 2‐fold in the presence of the modifier. Rheological measurements show a higher molecular weight in copolymers synthesized using modified methylaluminoxane. The alternative and dyad block microstructures of copolymers become possible in the case of a norbornene content of more than 14 mol%. Second, the effect of co‐monomer content on the rheological and thermal behavior of the synthesized copolymers was investigated. The results of the rheological study indicate a lower molecular weight in samples containing a higher norbornene content. Dynamic mechanical thermal analysis confirms the influence of different microstructures on the glass transition temperature. The crystal structure of copolymers having a higher molecular weight is emphasized using wide angle X‐ray scattering and DSC even with a greater incorporation of norbornene. © 2015 Society of Chemical Industry     

Impact of Site-Specific Benzo[a]Pyrene Diol Epoxide-dG Lesions at or near Single/Double-Strand DNA Junctions on DNA Bending

Adducts derived from the binding of the (+)-7R,8S,9S,10R and (?)-7S,8R,9R,10S enantiomers of r7,t8-dihydrodiol-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) to 2′-deoxyguanosine residues in DNA are known to induce mutations due to error-prone DNA replication. Because the conformational properties of these lesions may be important in these phenomena, we have examined the effects of the stereoisomeric (+)- and (?)-trans-anti-[BP]-N ²-dG lesions positioned site-specifically at or near primer/template oligonucleotide junctions on DNA bending using high resolution gel electrophoresis. Remarkable differences in electrophoretic mobilities μ are observed in the two adducts derived from the tumorigenic (+)-anti-BPDE, and the non-tumorigenic (?)-anti-BPDE enantiomer. With the (+)-trans lesion positioned on the template strand adjacent to the 3′-end of the primer strand, a remarkable decrease in μ is observed. This suggests the existence of a bend at the single strand-double strand junction. Only modest decreases in μ are observed in the case of the (?)-trans lesion, or when the 3′-end is opposite to, or more distant from the lesion site. These observations are discussed in terms of the known NMR solution structures of these lesions in the same sequence context, and the properties of primer/template DNA in polymerases.     

Synthesis of Dihydrodiol Metabolites of Naphtho[8,1,2- GHI ]Chrysene and Dibenzo[ C,MNO ]Chrysene

Syntheses of naphtho[8,1,2- ghi ]chrysene (naphtho[1,2- e ]pyrene, N[ e ]P) 1 , dibenzo[ c,mno ]chrysene (naphtho[1,2- a ]pyrene, N[ a ]P) 2 and their dihydrodiol metabolites are described. The hydrocarbons N[ e ]P 1 and N[ a ]P 2 and their fjord region dihydrodiols 12 and 19 were synthesized using a Suzuki cross-coupling reaction followed by the appropriate manipulation of the functional groups. The K-region cis dihydrodiols of N[ e ]P-4,5-diol 20 , N[ a ]P-4,5-diol 23 , N[ a ]P-7,8-diol 24 were obtained by OsO 4 oxidation. The cis diols thus obtained were first converted to the corresponding quinones with pyridinium chlorochromate and, finally, to the desired trans dihydrodiols 22 , 27 , and 28 by NaBH 4 reduction. The mixture of trans N[ a ]P-4,5- and 7,8-dihydrodiols was separated by high-performance liquid chromatography.     

Comparison of the Morphological Transforming Activities of Fjord-Region PAHs with Dibenzo[a,e]Pyrene and Benzo[a]Pyrene

The morphological transforming activities in mouse embryo C3H10T1/2CL8 (C3H10T1/2) cells were examined for six PAHs: benzo[c]chrysene (B[c]C); benzo[g]chrysene (B[g]C); benzo[c]phenanthrene (B[c]P); dibenzo[a, l]pyrene (DB[a, l]P); dibenzo[a,e]pyrene (DB[a,e]P) and benzo[a]pyrene (B[a]P). C3H10T1/2 cells treated with B[c]P or B[g]C at concentrations of 0–3 μg/ml did not produce any transformed Type II or III foci after 24 hr of exposure. Concurrent cytotoxicity was observed. Under the same conditions, B[a]P and B[c]C were active, with B[c]C approximately one-half the activity of B[a]P. However, after a 48-hr treatment, B[c]P and B[g]C gave significant activity measured as both foci/dish or the number of dishes exhibiting foci. After a 24-hr treatment, comparison of B[a]P with two dibenzopyrenes, DB[a, l]P and DB[a,e]P, gave activities in the order: DB[a, l]P > B[a]P > DB[a,e]P. After 48 hr of treatment, both B[a]P and DB[a,e]P had similar activities.