mirzaagha babazadeh

In the recent decade, the design and engineering of novel drug delivery systems based on biodegradable nanoparticles using biocompatible polymers like poly (ε-caprolactone)/poly(ethylene glycol)/poly(ε-caprolactone) triblock copolymer (PCEC) attracted many attentions. These nanocarriers have shown high potentials in enhancing treatment efficiency and minimizing the side effects of drugs. Besides, combination therapy has become a potential approach for cancer treatment with synergistic impacts. For the first time, we investigated co-delivery of the antitumor drug, doxorubicin (DOX), and ezetimibe (EZ) as a cholesterol uptake-blocking drug with PCEC on prostate cancer cell line (PC3). The PCEC was synthesized by ring-opening polymerization of ε-CL initiated by PEG2000. The obtained copolymer was characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR) spectroscopy, and gel permeation chromatography (GPC). In this study, DOX and EZ were encapsulated within PCEC by double and simple emulsion techniques, which led to the preparation of DOX@PCEC, EZ@PCEC, and DOX+EZ@PCEC nanoparticles. The size and morphology of the developed nanoparticles were analyzed by field emission scanning electron microscopy (FE-SEM). Also, the particle size and zeta potential of the drug-loaded PCEC nanoparticles were determined by dynamic light scattering (DLS) analysis . The release behavior of DOX and EZ from nanoparticles at two pH values and temperatures was evaluated. The cytotoxicity of nanoparticles was demonstrated by MTT assay using PC3 prostate cancer cell line. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the growth of the PC3 cell line. Therefore, PCEC is a biocompatible and suitable nano-vehicle for this study. Moreover, the cytotoxic activity of all formulations was dose-dependent. The cytotoxic effect of DOX+EZ@PCEC nanoparticles against PC3 cell line was higher than single drug@PCEC nanoparticles. All data confirmed that the EZ as a cholesterol-lowering drug showed a synergistic effect in combination with DOX as an anticancer drug. Finally, the results showed a successful formulation of DOX+EZ@PCEC nanoparticles with high efficiency in prostate cancer treatment.

One of the most potentially hazardous diseases, prostate cancer has a high morbidity and mortality rate. Polymeric matrix drug-eluting implants have become widely employed, and modeling their behavior is becoming more and more prominent. It is always difficult to achieve effective drug delivery and release of it into specific tumor sites. One of the most significant purposes of this investigation, is the enhancement of the anticancer effects of prostate cancer treatment by co-delivering anticancer multi-drugs with PU-PCL films. The films were recognized utilizing SEM  (scanning electron microscopy) while the material was being characterized. In addition, the MTT assay and flow cytometry (Annexin V/PI staining) have been employed to assess cell viability at various times. A dialysis approach was used to investigate the drug release characteristics of DOX and Ezetimibe in films in vitro for 5 days. To optimize pharmacokinetic profiles and reduce systemic toxicity induced by drugs, we loaded polymeric PU-PCL films with ezetimibe (EZ) and doxorubicin (DOX). Co-delivery of EZ and DOX via film-carrier demonstrated improved anticancer effects when compared to free drug delivery. The co-delivery of DOX and EZ drugs by PU-PCL films improved anticancer effects while reducing systemic toxicity, suggesting clinical usage of drug-resistant prostate cancer therapy.

In this research work, a serious of novel polymeric prodrugs of mefenamic acid was prepared in order to minimize of the mefenamic acid side effects. Glycidyl methacrylate was first copolymerized with acrylamide and methyl methacrylate by free radical solution polymerization method, using α,ά-azobisisobutyronitrile as an initiator at 70±2 oC. Mefenamic acid, as a non-steroidal anti-inflammatory drug, was then attached to the synthesized copolymers via the hydrolysable ester bonds by transesterification procedure in the presence of N,N'-dicyclohexylcarbodiimide to give polymeric prodrugs. The synthesized copolymers and polymeric prodrugs were characterized by various techniques such as FT-IR, 1HNMR and 13CNMR to confirm their structures. These polymeric prodrugs were hydrolyzed in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 1, 7.4 and 8.5) at 37 oC. Analysis of the hydrolyzing solutions by UV spectrophotometer at selected intervals showed that the drug could be released by selective hydrolysis of the ester bond from side chain of drug moiety. The release profiles of drug indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the hydrophilicity of polymer and the release rate of mefenamic acid at alkaline medium is higher than other mediums. These developed systems would be useful for the development of pH-sensitive polymeric prodrugs in controlled release systems.

Nano-sized of a copper (II) coordination polymer [Cu3(L)(NO3)4(H2O)4]n (1) {H2L=[2,6-bis(pyridine-2-ylmethylidene) hydrazinocabonyl] pyridine} compound was synthesized by sonochemistry method. To study the influence of solvent and concentrations of initial reagents on the nano-sized compound (1) certain test was designed and six samples of 1 were prepared through the sonochemical irradiation process. Polar solvent led to smaller and uniform nanostructure particle morphology. To prepare copper (II) oxide nano-sized by calcination specimen of 1 was used as a precursor. The structure and morphology of nanoparticles are characterized by using scanning electron microscopy (SEM), x-ray powder diffraction (XRD) and IR spectroscopy. The thermal stability of nano compound 1 was studied by thermal gravimetric (TGA) and differential thermal analyses (DTA). In order to study the optical behavior of the prepared compound 1 as nanoparticle and bulk form the UV-Vis absorption spectral along with photoluminescence was carried. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to analyze the intermolecular interactions, indicating that the most important contributions for the crystal packing are from O…H/H…O (31.7%), H…H (14.6%), C…C (6.5%), N…O (3.8%) and N…H/H…N (3.8%).

In this work, the potentials of Sc-, Ti-, and Zn-doped BN nanosheets for adsorbing and detecting the amantadine drug were studied by using density functional theory (DFT), natural bond orbital (NBO), and quantum theory of atoms in molecules (QTAIM). The amantadine adsorption on the considered doped BNNSs was chemisorption. The strongest adsorption was related to the amantadine adsorption on Sc-doped BNNS. Among the considered doped BNNSs, only Sc-doped BNNS can be employed as a suitable electronic conductivity detector for amantadine in the environment. In addition, all the considered doped BNNSs, may be proper for work function type in detecting the drug.

Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment.

In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures.

The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells.

Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.

AbstractIn this research, density functional theory (DFT) calculations were carried out for investigating the adsorption of the K atom and ion on the surface of three sheet-like nanoparticles, namely nanosheet, corannulene (CRN) and sumanene (SMN). Density of states (DOS) diagrams, geometry optimizations and total energies were all studied using the M06−2X level of theory with the basis set 6−31+G (d, p). The Ead for SMN-i was found to be more negative, which increased in the following order: SMN-i > nano-sheet > CRN-i > CRN > SMN. The main goal of this work was to compute the cell voltage (Vcell) for K−ion batteries (KIBs). Here, the Vcell for SMN was the highest value, which increased in the following order: SMN > CRN > nano-sheet > SMN-i > CRN-i. The current study provided a theoretical description and promising candidate of the above mentioned nano-structures as anode materials in KIBs ion batteries.

Mesoporous silica nanoparticles (MSNs) have drawn substantial interest as drug nanocarriers for breast cancer therapy. Nevertheless, because of the hydrophilic surfaces, the loading of well-known hydrophobic polyphenol anticancer agent curcumin (Curc) into MSNs is usually very low.

For this purpose, Curc molecules were loaded into amine-functionalized MSNs (MSNs-NH2-Curc) and characterized using thermal gravimetric analysis (TGA), Fouriertransform infrared (FTIR), field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET). MTT assay and confocal microscopy, respectively, were used to determine the cytotoxicity and cellular uptake of the MSNs-NH2- Curc in the MCF-7 breast cancer cells. Besides, the expression levels of apoptotic genes were evaluated via quantitative polymerase chain reaction (qPCR) and western blot.

It was revealed that MSNs-NH2 possessed high values of drug loading efficiency and exhibited slow and sustained drug release compared to bare MSNs. According to the MTT findings, while the MSNs-NH2-Curc were nontoxic to the human non-tumorigenic MCF-10A cells at low concentrations, it could considerably decrease the viability of MCF-7 breast cancer cells compared to the free Curc in all concentrations after 24, 48 and 72 hours exposure times. A cellular uptake study using confocal fluorescence microscopy confirmed the higher cytotoxicity of MSNs-NH2-Curc in MCF-7 cells. Further, it was found that the MSNs-NH2-Curc could drastically affect the mRNA and protein levels of Bax, Bcl-2, caspase 3, caspase 9, and hTERT relative to the free Curc treatment.

Taken together, these preliminary results suggest the amine-functionalized MSNsbased drug delivery platform as a promising alternative approach for Curc loading and safe breast cancer treatment.

This study deals with the interaction between the Amantadine drug (Ad) and the Boron Nitride NanoSheet (BNNSh). The interactions between the Ad molecule and BNNSh, doped Si-BNNSh, Ge-BNNSh, and Ga-BNNSh were carried out at the RCAM-B3LYP method with 6-31G(d) basis set using the Gaussian 09 program. The DFT calculations clarified a weak interaction between the Ad drug and BNNSh. The doped Si, Ge, and Ga-BNNSh were examined to obtain a suitable interaction between the Ad drug and BNNSh to make a suitable sensing device. The adsorption energy (Ead), as well as the gap energy between HOMO and LUMO (Eg), were calculated for the Ad drug and BNNSh and its doped Si-, Ge-, and Ga-BNNSh. The DFT calculations indicated that the Ead of the Ge-BNNSh/Ad complex is -19.67 which was suitable adsorption energy for the sensing ability with low recovery time. Also, the change of % ΔEg for the Ge-BNNSh/Ad is -21.50% which shows a high sensitivity of Ge-BNNSh to the Ad drug. This study showed that Ge-BNNSh is a promising candidate for being a possible sensor of the Ad drug.

Today, increasing attention is being paid to the application of biocompatible polymers as drug carriers with low cytotoxicity in drug delivery systems to enhance the therapeutic effects of anticancer agents.
In this study, a biocompatible synthetic polymer (grafted on graphene oxide), composed of N-isopropylacrylamide and 1-vinyl-2-pyrrolidone with L-lysine segments (Lys/PNIPAM-PVP/GO), was developed as a nano-vehicle for the drug. This platform was used for the delivery of fluorouracil (FU) to A549 human lung cancer cells. The superior characteristics of the platform included low-cost precursors, easy synthesis, and the presence of many functional groups for loading drugs. To determine and compare the cytotoxic effects of free FU and its formulated form on the A549 cells, MTT assay was performed; the results showed no significant toxicity difference between the two treated groups (free and formulated FU).
For further evaluations, cellular uptake assays were performed via fluorescence microscopy and flow cytometry.
Both analyses revealed the low internalization of nano-vehicle into the A549 cells, with 4.31% and 8.75% cellular uptakes in the first two and four hours of treatment. Therefore, the low penetration rate reduced the toxicity of drug-loaded nano-vehicle.
Finally, DAPI staining and Annexin V-FITC staining were performed as complementary techniques to determine cell apoptosis

In this work, the interactions between the Na neutral atom and Na+ ion and three nanostructures such as sumanene (SM), corannulene (CN), and nanosheet were investigated. The main goal of this work is to calculate the cell voltage (V) for Na−ion batteries, NIBs. The total energies, geometry optimizations, and density of states (DOS) diagrams were studied by using M06−2X level and 6−31+G(d,p) basis set. The DFT calculations indicated that the energy adsorption between Na+ ion and nanostructures, Ead,were increased in the order: SM-i > Sheet > CN-i > CN > SM. Nevertheless, the Vcell for SM has obtained the highest value. The Vcell of NABs are increased in the order: SM > CN > Sheet > SM-i > CN-i. This research theoretically described the possible uses of the mentioned nanostructures as anode the anodes in Na−ion Batteries.

A new series of crown ether-based macrocycles bearing two hydroxyl groups and a dibenzosulfoxide moiety was synthetized. These symmetrical dibenzosulfoxo- (aza)-crown ethers were synthesized by the reaction of an active symmetrical bisepoxide pod and with diol reagents in the presence of sodium hydride as a strong base and dry tetrahydrofuran as the solvent. In fact, the reaction begins with the opening of the epoxide rings via the nucleophilic attack (SN2) of dialkoxide and ends with the formation of a macrocyclic ring. The final compounds were characterized by FT-IR, 1H NMR, 13C NMR, and FAB-MS spectroscopic methods. They were evaluated for their extraction ability and selectivity for various metallic cations in the form of picrate salt in dichloromethane solvent at room temperature. The new macrocycles showed good extraction ability especially for Pb2+ (72%), K+ (66%), and Ba2+ (56%) among the used cations, for 3b, 3c, and 3a respectively. Compound 3b (dibenzosulfoxo-20-aza-crown-4-ether) showed the excellent selectivity for Pb2+ (72%).

The present research work describes an efficient method for facile synthesis of α-MnO2 nanorods by hydrothermal method and preparation of a series of polythiophene/manganese dioxide (PTh/MnO2) nanocomposites with various α-MnO2 ratios. These nanocomposites were fabricated by in-situ oxidative polymerization method using FeCl3 as oxidant, and characterized by Fourier transformed infrared (FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray (EDX), thermogravimetric thermal analyses (TGA), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques. FT-IR, EDX and XRD data showed that as-synthesized α-MnO2 nanorods has been definitely incorporated into the polymer matrix via in-situ core-shell polymerization. SEM and TEM pictures showed that the nanocomposites have rod-like morphology with the average diameter of 50-70 nm. TGA measurements showed that introducing α-MnO2 nanorods into PTh matrix, improve the thermal stability of nanocomposites in comparison with pure PTh. This employed method is very simple and inexpensive in comparison with methods applied by other researchers, and it can be easily applied industrially.

Abstract-4-(3-(2,4-Dichlorophenyl)triaz-1-enyl)benzamide, CTB, was synthesized and characterized using IR and NMR (1H and 13C) spectroscopy. The optimized geometry, vibrational wave numbers, 1H and 13C chemical shift values and NBO parameters of CTB were computed with Density Functional Theory (DFT/PBE1PBE) and Hartree-Fock (HF) methods using 6-311+G(2d,p) basis set. The harmonic vibrational wavenumbers were calculated and their scaled values were compared with the experimental FT-IR spectrum. A detailed interpretation of the NMR spectra of CTB was reported. The calculated data are in reasonably good agreement with the experimental measurements. Moreover, the logP value and thermodynamic properties were estimated with ChemBioOffice Ultra 11.0, ACD/LogP and ALOGPS programs. The NBO analysis was carried out for CTB.

Efficient and environmentally friendly syntheses of xanthenes derivatives by using γ-Fe2O3@HAP-Fe2+ NPs as a catalyst has been carried out. The catalyst can be readily isolated by using an external magnet and no obvious loss of activity was observed when the catalyst was reused in eight consecutive runs. The procedure has several advantages, such as economic availability of catalyst, simple procedure, ease of product isolation, no harmful byproducts, less reaction time and high yields.

Functionalized morpholines have attracted much attention due to their potential biological activities. Despite the wide importance of morpholine derivatives in drug design of various pharmacological agents, the development of new approaches to their synthesis remains relatively unexplored.
Given the low cost and easy availability of N-propargylamines, the synthesis of functionalized morpholines from these versatile building blocks have undergone an explosive growth in recent years. This review provides a concise overview of the synthesis of morpholine cores from N-propargyalamines in recent years.

This research work, describes synthesis and in vitro evaluation of a serious of new acrylic type polymeric prodrugs containing 5-aminosalicylic acid (5-ASA), an important drug in the treatment of inflammatory bowel diseases, as colon targeted drug delivery systems. First, 5-ASA reacted with formic acid to obtain 5-formylaminosalicylic acid in the high yield. Reaction of the obtained material with 2-hydroxypropyl methacrylat in the presence of 1,1 carbonyldiimidazole produced methacryloyloxypropyl-5-aminosalicylate (MOPAS), as a acrylic-derivative of 5-ASA, in a one-pot procedure. The resulted MOPAS was then polymerized with hydrophilic and hydrophobic acrylic-monomers such as 2-hydroxyethyl methacrylat, methyl metacrylat or ethylhexyl acrylate by free radical polymerization method to obtain polymeric prodrugs bearing 5-ASA. All compounds were characterized by FT-IR, 1H NMR, elemental analysis and gel permeation chromatography techniques. Also, thermal behavior of the polymeric prodrugs was investigated by differential scanning calorimeter instrument. The release studies of 5-ASA were performed into dialysis bags by hydrolysis buffered solutions (pH 1, 7, 8) at 37°C. Detection of hydrolysis by UV spectroscopy at selected interval showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behavior of polymeric prodrugs is strongly based on the hydrophobicity of polymers and the pH of the hydrolysis media. The results suggested that these systems could be useful in colon targeted drug delivery systems.

Vinyl ester polymeric systems linked to ibuprofen were synthesized and evaluated as materials for drug delivery. The carboxyl group of ibuprofen was converted into vinyl ester group by reacting ibuprofen with vinyl acetate in the presence of mercuric acetate as a catalyst. The resultant ibuprofen derivative of vinyl ester was then copolymerized with 2-hydroxyethyl methacrylate or methyl methacrylate (in 1:3 mole ratios) by utilizing azoisobutyronitrile as an initiator at the temperature range of 65-70ºC. The structure of all compounds was characterized and confirmed by FTIR, 1H NMR, and 13C NMR spectroscopy techniques and elemental analysis. Gel permeation chromatography was used for determination of the average molecular weights and polydispersity indices of the ibuprofen containing polymers. The hydrolysis of drugpolymer conjugates was carried out in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 1, 7.4, and 10) at 37ºC for 48 h. Detection of hydrolysis solutions by UV-vis spectroscopy at selected intervals showed that the drug could be released by hydrolysis of the ester bonds which were formed between the drug and polymer backbone. The release profiles indicated that the hydrolytic behaviour of polymeric prodrugs is strongly based on polymer hydrophilicity and pH of the hydrolysis solution. The results suggest that these prepared polymeric prodrugs could be useful for release of ibuprofen in controlled release systems.

Acrylic-type polymeric systems having degradable ester bonds linked to ibuprofen were synthesized and evaluated as materials for drug delivery. Ibuprofen, as a non-steroidal anti-inflammatory drug, was linked to 2-hydroxyethyl methacrylate by activated ester methodology in one-pot procedure. The resulting methacrylic derivative of ibuprofen was copolymerized with 2-hydroxyethyl methacrylate and n-butyl acrylate (in 1:3 mole ratio) by free radical polymerization method in N,N-dimethylformamide solution, utilizing azoisobutyronitrile as initiator at 65-70 oC. All of the obtained compounds were characterized by FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis technique. The average molecular weights of the polymers bearing ibuprofen were determined by gel permeation chromatography and their polydispersity indices resulted in the range of 1.8-1.9. Release studies of ibuprofen were performed into dialysis bags by hydrolysis in buffered solutions (pH 1, 7.4 and 10) at 37 oC. Detection of hydrolysis by UV spectroscopy at selected intervals showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behaviour of polymeric prodrugs is strongly based on the polymer hydrophilicity and the pH value of the hydrolysis solution. The results suggest that these polymeric prodrugs could be useful for release of ibuprofen in controlled release systems.

Polyaniline (PANI) doped with dodecyl benzene sulphonic acid (DBSA) was directly synthesized by aniline polymerization in the presence of DBSA in an aqueous medium. The temperature and colour changes of the polymerization reaction were carefully recorded and found that the polymerization of aniline begins after 80 min with changing reaction colour from white to pale blue. Fourier transform infrared (FTIR), elemental analysis, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques were used to characterize and analyze the thermal characteristics of the doped PANI sample. In the FTIR spectrum, the peak related to NH+…SO3 - interactions between the polymer chain and the dopant appeared at 1026 cm-1. The obtained TGA curve has illustrated three major stages in the weight loss of the doped PANI. These three weight loss stages were accounted to the evaporation of moisture, evaporation of DBSA, and the chemical structure degradation of PANI. The moisture, DBSA, and PANI contents ofthe product were calculated from TGA curve and it was shown that approximately 6.65aniline repeating units have been doped with one DBSA molecule. The DSC thermogramhas shown two endothermic peaks around 120ºC and 280ºC due to the evaporationsof moisture and DBSA, respectively. The analysis of XRD spectra confirmedthat a chemical cross-linking reaction occurs between the PANI chains during thermaltreatment and increases the amorphous state of the sample. The resultant electricalconductivity examination at the heating temperature of 100ºC has shown that at theheating time of 30 min the doped PANI possessed maximum electrical conductivitywhich decreased by increase in heating time.