...funding research, sharing discoveries.
Rassoul Dinarvand
Professor and Dean, Faculty of Pharmacy, Tehran University of Medical Sciences
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International journal of nanomedicine 5
Physicochemical and biological properties of self-assembled antisensepoly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio.
To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple metho... expand abstractds were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer. AFM images also showed that such nanoparticles were spherical. The stability of the antisense content of the nanoparticles was investigated over different charge ratios using polyacrylamide gel electrophoresis. It was clear from such analyses that much more than charge neutrality point was required to obtain stable nanoparticles. For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5'-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture. This investigation also shows that the cytotoxicity of the nanoparticles was dependent upon the generation and charge ratio of the PAMAM dendrimer, and the antisense concentration had no significant effect on the cytotoxicity. collapse abstract
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PDA journal of pharmaceutical science and technology / PDA 63(6)
Preparation and characterization of poly lactide-co-glycolide nanoparticles of SN-38.
SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan (CPT-11), which is 100-1000-fold more cytotoxic than irinotecan. Nonetheless, the extreme hydrophobicity of SN-38 has prevented its clinical use. SN-38 is poorly soluble in... expand abstract aqueous solutions, and it is practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. One way of improving the solubility and stability of SN-38 is to formulate the drug into nanoparticles. Incorporation of cytotoxic agents into nanoparticles has also shown increased toxicity. In this study, poly lactide-co-glycolide was used for the preparation of nanoparticles of SN-38. The nanoparticles were fabricated by an emulsification/solvent evaporation method. The effect of several variables on nanoparticle characteristics was evaluated, including the ratio of drug-polymer, the amount of the poly vinyl alcohol as surfactant, and the internal phase volume/composition. The SN-38 encapsulation efficiency and the particle size distribution were optimized by varying these parameters. Nanoparticles were spherical with a relatively mono-dispersed size distribution. As the ratio of acetone to dichloromethane increased, a considerable decrease in the particle size of nanoparticles was achieved. The encapsulation efficiency of all samples was more than 80%. Changing the poly vinyl alcohol concentration in the external phase had some effects on size and morphology and encapsulation efficiency. It was shown that SN-38 nanoparticles are considerably stable in a long-term stability study. collapse abstract
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Anti-cancer drugs 2009 Dec; 21(1)
Cellular cytotoxicity and in-vivo biodistribution of docetaxel poly(lactide-co-glycolide) nanoparticles.
Docetaxel (DTX) is one of the most effective antineoplastic drugs. However, its current clinical administration, formulated in tween80, causes serious side effects. This study is focused on preparation and evaluation of poly(lactide-co-glycolide) nan... expand abstractoparticles (NPs) containing DTX to remove tween80. Drug encapsulation efficiency, in-vitro drug release, cellular cytotoxicity, and in-vivo biodistribution of NPs in mice after intravenous administration were investigated. The average diameter of the NPs was approximately 172-178 nm with encapsulation efficiency of 68%. A burst release of approximately 30% (w/w) of the loaded drug followed by a sustained release profile was observed. Cellular mortality of the NPs was more than or at least as great as DTX free drug; for example, cell viability measured at 100 nmol/l drug concentration was decreased from 50.9% for DTX free drug to 15.9% for the NP formulation after 48 h incubation with T47D cells. The DTX plasma amount remained at a good level (13% of the initial dose) in the NP formulation compared with the DTX conventional formulation, which is approximately 0.5% of the initial dose, was present in plasma up to 2 h. Poly(lactide-co-glycolide) NPs containing DTX prepared in this study may be regarded as a suitable and superior formulation for the current formulation in the market containing tween80 with improved cancerous cell mortality and biodistribution characteristics. collapse abstract
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Journal of chromatography. A 2010 Apr; 1217(16)
Solid drop based liquid-phase microextraction.
Solid drop based liquid-phase microextraction (SDLPME) is a novel sample preparation technique possessing obvious advantages of simple operation with a high pre-concentration factor, low cost and low consumption of organic solvent. SDLPME coupled wit... expand abstracth gas chromatography (GC), high-performance liquid chromatography (HPLC), and atomic absorption spectrometry (AAS) has been widely applied to the analyses of a different variety of samples. The basic principles, parameters affecting the extraction efficiency, and the latest applications of SDLPME are reviewed in this article. collapse abstract
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Nanomedicine : nanotechnology, biology, and medicine 2010 May; 6(3)
Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines.
SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan, which is 100-to 1000-fold more cytotoxic than irinotecan. Nevertheless, extreme hydrophobicity of SN-38 has prevented its clinical use. One way of improving the solubility... expand abstract and stability of SN-38 is to formulate the drug into nanoparticles. Folic acid has been widely used as a targeting moiety for various anticancer drugs. For folate-receptor-targeted anticancer therapy, SN-38 nanoparticles were produced using poly-lactide-co-glycolide-polyethylene glycol-folate (PLGA-PEG-FOL) conjugate by emulsification/solvent evaporation method. The FOL-conjugated di-block copolymer was synthesized by coupling the PLGA-PEG-NH(2) di-block copolymer with an activated folic acid. The conjugates were used for the formation of SN-38 nanoparticles with an average size of 200 nm in diameter. The SN-38 targeted nanoparticles showed a greater cytotoxicity against HT-29 cancer cells than SN-38 nontargeted nanoparticles. These results suggested that folate-targeted nanoparticles could be a potentially useful delivery system for SN-38 as an anticancer agent. FROM THE CLINICAL EDITOR: SN-38 is the active metabolite of the chemotherapy agent irinotecan, which is 100-1000 fold more cytotoxic than irinotecan, but its extreme hydrophobicity has prevented its clinical use. In this paper, the authors present a nanotechnology-based approach targeting the folate-receptor with SN-38 loaded nanoparticles, demonstrating stronger cytotoxicity against HT-29 cancer cells than with control nanoparticles. collapse abstract
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Talanta 2009 Dec; 80(2)
Quantitation of atorvastatin in human plasma using directly suspended acceptor droplet in liquid-liquid-liquid microextraction and high-performance liquid chromatography-ultraviolet detection.
A simple and sensitive methodology based on liquid-liquid-liquid microextraction (LLLME) followed by high-performance liquid chromatography-ultraviolet detection (HPLC-UV) has been successfully developed for the determination of atorvastatin (AT) in ... expand abstracthuman plasma. AT was first extracted from 4.5 mL acidic aqueous sample (diluted plasma, donor phase, pH 1) at temperature 45 degrees C through 400 microL 1-octanol for 4.5 min, while being agitated by a stirring bar at 1250 rpm. Then, a 5.5 microL free suspended basic aqueous droplet (acceptor phase, pH 10) was delivered to the top-center position of the organic membrane. The mixture was stirred at 650 rpm for 7.5 min and the analyte was back-extracted into the droplet. Finally, the acceptor phase was taken into a microsyringe and injected directly into the HPLC. An enrichment factor of 187 along with substantial sample clean up was obtained under the optimized conditions. The calibration curve showed linearity in the range of 1-500 ng mL(-1) with regression coefficient corresponding to 0.996. Limits of detection (S/N=3) and quantification (S/N=10) were 0.4 and 1 ng mL(-1), respectively. A reasonable relative recovery (91%) and satisfactory intra-assay (4.4-7.0%, n=6) and inter-assay (4.9-7.7%, n=8) precision illustrated good performance of the analytical procedure. This technique was eventually applied for the determination of AT in human plasma after oral administration of 40 mg single dose of drug. The protocol proved to be highly cost-effective and reliable for the screening purpose. collapse abstract
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Journal of pharmaceutical sciences 2009 Jul; 98(8)
Docetaxel-albumin conjugates: preparation, in vitro evaluation and biodistribution studies.
Docetaxel (DTX) is one of the most active chemotherapeutic agents for treating metastatic breast cancer. Its aqueous solubility is very low, hence the available formulation of DTX for clinical use consists of high concentrations of tween80, which has... expand abstract been associated with several hypersensitivity reactions. To reduce the systemic toxicity of DTX as well as to avoid the use of tween80, in this study DTX was chemically conjugated with human serum albumin via a succinic spacer. A high-performance liquid chromatography method was developed for the determination of DTX-albumin conjugate. T47D and SKOV3 cells were used for the evaluation of the in vitro cytotoxicity of the conjugate by MTT assay. Studies were then done on balb/c mice to elucidate the tissue distribution of conjugates after intravenous administration. The albumin-conjugated formulation of DTX with the particle size of 90-110 nm showed enhanced solubility and in vivo characteristics and significantly higher cytotoxicity against tumor cells, for example, IC50 of 6.30 +/- 0.73 nM for T47D cell line compared to free DTX with IC50 of 39.4 +/- 1.75 nM. Conjugation also maintained DTX plasma level at 16.19% up to 2 h after injection compared with 2.51% for Taxotere, hence increasing the chance of nanoparticles uptake by tumor cells. collapse abstract
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Journal of chromatographic science 2009 Jul; 47(7)
Development and validation of a stability-indicating method for the quantitation of Paclitaxel in pharmaceutical dosage forms.
A simple, rapid stability-indicating isocratic assay has been developed and validated for the determination of Paclitaxel (PTX) in commercial injection formulations. The assay is performed using a Nucleosil RP-18 (5 microm, 250 x 4.0 mm i.d) column p... expand abstractrotected by a Nucleosil C(18) precolumn (5 microm, 4.0 x 4.0 mm i.d.) with a mobile phase of methanol-water (80:20) and UV detection at 230 nm. The method was found to be specific for PTX in the presence of degradation products with an overall analytical run time of ~ 9 min. Accuracy reported as % bias was found to be 0.1-2.5% bias for all samples tested. Intra-assay precision (repeatability) was found to be 0.22-2.65% RSD, while inter-day precision (intermediate precision) was found to be 1.0-3.0% RSD for the samples studied. The calibration curve was found to be linear with the equation y = 29.78x + 7.65, and a linear regression coefficient of 0.9994 over the concentration range 0.05-20 microg/mL. The limits of quantitation and detection were 0.05 and 0.02 microg/mL, respectively. Taxol (30 mg/5 mL), a commercially available dosage form of PTX, was assayed and 100.6-103.6% of the label claim was recovered. collapse abstract
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Journal of nanoscience and nanotechnology 2009 Jul; 9(8)
Thiolated chitosan nanoparticles as an oral delivery system for Amikacin: in vitro and ex vivo evaluations.
The purpose of this study was the synthesis of two thiol conjugated Chitosan polymers, and evaluation of the potential of Thiomer nanoparticle formulation as a carrier for oral delivery system. Mediated by EDAC (Ethylene-3-(3-di-methylaminopropyl)-ca... expand abstractrbodiimide), either N-acetyl Cysteine (NAC) or N-acetyl D-penicillamine (NAP) were covalently attached to Chitosan. The success of the synthesis was demonstrated by comparing FTIR spectra. Iodometric titration demonstrated that depending on the pH value of the synthesis medium, the Thiomers display 250 +/- 30 microMol and 300 +/- 20 microMol thiol groups per gram of polymer respectively. The interaction between mucin and Thiomers, compared to mucin and Chitosan was studied for assessment of mucoadhesion properties of synthesized polymers. This interaction was determined by the measurement of the amount of mucin adsorbed on Chitosan and the conjugated polymers. Rotating cylinder method demonstrated an average of 20 times improvement in mucoadhesion of Thiomers compared to the unmodified polymer. Chitosan and Thiomer nanoparticles were formulated by two methods; TPP and Sodium Sulfate gelation. SEM micrographs and data achieved by a Malvern nano/zetasizer show nanoparticles formed by TPP gelation have a mean size of 150 +/- 15 nm compared to 300 +/- 25 nm sized nanoparticles obtained by Sodium sulfate gelation. TPP gelation yields smaller, more spherical shaped nanoparticles with a smaller range of size distribution. Amikacin loaded nanoparticles with an average size of 280 nm were prepared by TPP gelation in which disulfide bond formation was achieved by a time dependent oxidation process. In vitro studies were carried out; a recovery rate of 33% and a drug entrapment of 25% were achieved. The amount of release was determined during 18 hr in a carefully prepared media. The permeation time across a biological membrane was observed to be about 150 minutes. Microbiological tests were carried out on two microorganisms; Pseudomona aeruginosa and Staphylococcus aureus to further confirm the amount of Amikacin inside drug loaded nanoparticles. collapse abstract
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Chemical biology & drug design 2009 Jul; 74(2)
Quantitative structure-activity relationship study on the anti-HIV-1 activity of novel 6-naphthylthio HEPT analogs.
The quantitative structure-activity relationship of the novel 6-naphthylthio 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio) thymine derivatives for prediction of anti-human immunodeficiency virus type 1 activity was studied. The suitable set of the molec... expand abstractular descriptors was calculated and the important descriptors using the variable selections of the stepwise multiple linear regression and the genetic algorithm were selected. A comparison between the attained results indicated the superiority of the genetic algorithm over the stepwise multiple regression method in the feature-selection. The predictive quality of the quantitative structure-activity relationship models was tested for an external set of eight compounds, randomly chosen out of 39 compounds. The genetic algorithm-multiple linear regression model with six selected descriptors was obtained. This model, demonstrating high statistical qualities (R(2)(train) = 0.925, Q(2) = 0.872, SE (%) = 1.23, F = 49.338, R(2)(pred) = 0.944), could predict the anti-human immunodeficiency virus type 1 activity of the molecules with a prediction error percentage lower than 10%. The results suggest that electronegativity, the masses, and the atomic van der Waals volumes are the main independent factors contributing to the anti-human immunodeficiency virus type 1 activity of the studied compounds. collapse abstract
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Bioprocess and biosystems engineering 2010 Feb; 33(3)
Investigation of chromatography and polymersalt aqueous two-phase processes for downstream processing development of recombinant phenylalanine dehydrogenase.
This work presents a comprehensive study between the polymer/salt aqueous two-phase systems (ATPS) and chromatography process for downstream processing of recombinant Bacillus badius phenylalanine dehydrogenase (PheDH). First, the partitioning behavi... expand abstractor of recombinant PheDH in polyethylene glycol (PEG)/K2HPO4 ATPS was examined. For comparative purpose, a classical chromatographic protocol was performed as well. Investigation of chromatography and ATPS procedures revealed that the ATPS comprising of 9% (w/w) PEG-6000, 16% (w/w) K2HPO4 and 16% (w/w) KCl with pH of 8.0, volume ratio (V ( R )) of 0.25, temperature of 25 degrees C and 40% (w/w) cell lysate ensured the most favorable approach for PheDH downstream process. A specific activity of 4,231.4 U/mg, a yield of 96.7% and a recovery of 162.0% were obtained. Furthermore, the shorter process time (4 vs. 48 h) and the lower total cost (4 vs. 20 euro) were additionally features that confirmed the suitability of proposed technique. collapse abstract
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Acta pharmaceutica (Zagreb, Croatia) 2009 May; 59(2)
Preparation of pegylated nano-liposomal formulation containing SN-38: In vitro characterization and in vivo biodistribution in mice.
7-Ethyl-10-hydroxy-camptothecin (SN-38), a metabolite of irinotecan x HCl, is poorly soluble in aqueous solutions and practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. Formulation of SN-38 in concentra... expand abstractted pharmaceutical delivery systems for parenteral administration is thus very difficult. Due to their biocompatibility and low toxicity, liposomes were considered for the delivery of SN-38. In this study, pegylated liposomes with distearoylphosphatidylcholine, distearoylphosphatidylethanolamine containing SN-38 were prepared and their characteristics, such as particle size, encapsulation efficiency, in vitro drug release and biodistribution, were investigated. The particle size of liposomes was in the range of 150--200 nm. The encapsulation efficiency and in vitro release rate of pegylated liposomes was higher than those of non-pegylated liposomes. As expected, the distribution of pegylated liposomes in body organs such as liver, kidney, spleen and lung was considerably lower than that of non-pegylated liposomes. Also, their blood concentration was at least 50 % higher than that of non-pegylated liposomes. collapse abstract
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Nanomedicine : nanotechnology, biology, and medicine 2010 Jan; 6(1)
Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method.
In the past decade, many strategies have been developed to enhance oral protein delivery. The aim of the current work was to develop a nanoparticulate system based on ionic gelation between chitosan and Arabic gum for loading of insulin. Various form... expand abstractulations were prepared using 2(3) factorial designs. The optimum association efficiency was obtained for formulations F2, F5, and F8. The release profile of insulin in phosphate buffer solutions (pH 6.5 and pH 7.2) is completely different than that in acidic medium (pH 1.2). Increased solubility of chitosan in acidic medium and better swelling of Arabic gum chains at pH >6.5 resulted in lower insulin release of nanoparticles at pH 6.5 in comparison with that of the other pH mediums. The values of the exponent n were 0.49 and 0.82 for formulations F8 and F5, respectively, indicating a non-Fickian transport. This suggests that release is possibly controlled by diffusion or relaxation of the polymer chains. FROM THE CLINICAL EDITOR: This paper summarizes the development of a nanoparticulate system based on ionic gelation between chitosan and gum Arabic for oral delivery of insulin. If preclinical studies in animal models will indicate reliable and quantifiable delivery of insulin, this method may pave the way to a novel and less invasive way of administering insulin to diabetes patients. collapse abstract
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Journal of agricultural and food chemistry 2009 Apr; 57(7)
Study on the performance of the headspace liquid-phase microextraction, gas chromatography-mass spectrometry in the determination of sorbic and benzoic acids in soft drinks and environmental water samples.
A simple, efficient and virtually solventless headspace liquid-phase microextraction (HS-LPME) technique, combined with gas chromatography-mass spectrometry (GC-MS), was developed for the analysis of sorbic acid (SA) and benzoic acid (BA) in soft dri... expand abstractnks and environmental water samples. A microdrop of organic solvent was suspended from the tip of a microsyringe needle over the headspace of the stirred sample solution, containing the analytes for a desired time. The microdrop was then retracted into the microsyringe and directly injected into the GC-MS, without any further pretreatment. Initially, microextraction efficiency factors were optimized, and the optimum experimental conditions found were as follows: 2.5 microL toluene microdrop exposed for 20 min over the headspace of a 6.5 mL aqueous sample (45 degrees C), containing 3 M of NaCl with pH of 1.5 and stirred at 1000 rpm. Under the optimized extraction conditions, preconcentration factors of 154 and 198, limits of detection of 0.3 and 0.1 microg L(-1) (S/N=3) with dynamic linear ranges of 1-500 and 0.5-500 microg L(-1), were obtained for SA and BA respectively. A good repeatability (RSD<10.3%, n=8) and satisfactory linearity (r(2) >or= 0.99) of results were achieved. The accuracy of the method was tested by the relative recovery experiments on spiked samples, with results ranging from 90 to 113%. The method proved to be rapid and cost-effective and is a green procedure for screening purposes. collapse abstract
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Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 2009 Mar; 25(4)
Application of adsorptive voltammetry for the detection of sub-nano molar cyclizine in biological fluids and tablets using fast Fourier transform continuous cyclic voltammetry in a flowing system.
An easy and fast Fourier transform continuous cyclic voltammetric technique (FFTCV) for monitoring of ultra trace amounts of cyclizine in a flow-injection system has been introduced in this work. The potential waveform, which was applied continuously... expand abstract on an Au disk microelectrode (12.5 microm in radius) consisted of the potential steps for cleaning, accumulation and potential ramp. The proposed detection method has some advantages, the greatest of which are as follows: first, it is no longer necessary to remove oxygen from the analyte solution and second, this is a very fast and appropriate technique for determination of the drug compound in a wide variety of chromatographic analysis methods. The detection limit for cyclizine was 1.8 ng ml(-1). The relative standard deviation (RSD) of the proposed technique at 5.0 x 10(-7) was 2.0 for 10 runs. The influences of pH of eluent, accumulation potential, sweep rate, and accumulation time on the determination of the cyclizine were considered. The proposed method was applied to the determination of cyclizine in a pharmaceutical preparation. collapse abstract
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Nanomedicine : nanotechnology, biology, and medicine 2009 May; 5(2)
Preparation and in vitro evaluation of mucoadhesion and permeation enhancement of thiolated chitosan-pHEMA core-shell nanoparticles.
The aim of the present work was to evaluate the in vitro mucoadhesion and permeation enhancement properties of thiolated chitosan (chitosan-glutathione) coated poly(hydroxyl ethyl methacrylate) nanoparticles. Core-shell nanoparticles were prepared by... expand abstract radical emulsion polymerization method initiated by cerium(IV) ammonium nitrate. Different molecular weights of chitosan were utilized for nanoparticles preparation. The physicochemical properties of nanoparticles were characterized by size, zeta potential, and thiol content. Incorporation of fluorescein isothiocyanate dextran (FD4, MW 4400 Da), which was used as the model macromolecule, was achieved by incubation method. The intestinal mucoadhesion and penetration enhancement properties of nanoparticles were investigated using excised rat jejunum. All nanoparticle systems showed mucoadhesion and improved apparent permeation coefficient (P(app)) of FD4. Nanoparticles prepared by thiolated chitosan with medium molecular weight revealed the most mucoadhesion and penetration enhancement properties. collapse abstract
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Journal of separation science 2008 Dec; 32(2)
Liquid-phase microextraction by solidification of floating organic microdrop and GC-MS detection of trihalomethanes in drinking water.
A simple and sensitive methodology based on liquid-phase microextraction (LPME) followed by GC-MS, was developed for the determination of trihalomethanes (THMs) in drinking water. A microdrop of organic solvent was floated on the surface of the aqueo... expand abstractus sample and it was agitated for a desired time. Then, the sample vial was cooled by inserting it into an ice bath for 4 min. The solidified solvent was transferred into a suitable vial and immediately melted. The extract was directly injected into the GC. Microextraction efficiency factors were investigated and optimized: 7 muL 1-undecanol microdrop exposed for 15 min floated on the surface of a 10.0 mL aqueous sample with the temperature of 60 degrees C containing 3 M of NaCl and stirred at 750 rpm. Under the selected conditions, enrichment factors (EFs) up to 482-fold, LOD of 0.03-0.08 mug/L (S/N = 3) and dynamic linear ranges of 0.10-100 mug/L were obtained. A reasonable repeatability (RSD < 8.6%, n = 8) with satisfactory linearity (r(2) greater, not dbl equals 0.9947) of results illustrated a good performance of the present method. The protocol proved to be rapid, cost-effective, and is a green procedure for the screening purposes. collapse abstract
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Chemical biology & drug design 2008 Nov; 72(6)
QSAR study of 2-(1-Propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide as PARP inhibitors for treatment of cancer.
Quantitative structure-activity relationship of the 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide as a potent inhibitor of poly(ADP-ribose) polymerase for cancer treatment was studied. A suitable set of molecular descriptors was calculate... expand abstractd and the genetic algorithm was employed to select those descriptors that resulted in the best fitted models. Excellent results were obtained employing multiple linear regressions and critically discussed using a variety of statistical parameters. Furthermore, the model was validated using leave-one-out and leave-group-out cross-validation, external test set and chance correlation. A genetic algorithm-multiple linear regression model with seven selected descriptors was obtained. This model, with high statistical significance (R(2) = 0.935, Q(2)_(LOO)= 0.894, Q(2)_(LGO)= 0.875, F = 53.481), could be used to predict poly(ADP-ribose) polymerase inhibitor activity of the molecules. collapse abstract
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Iranian journal of immunology : IJI 2008 Aug; 5(3)
Comparison of the adjuvanticity of aluminum salts and their combination in hepatitis B recombinant protein vaccine in assessed mice.
BACKGROUND: Several adjuvants have been evaluated for vaccine formulations but aluminum salts will continue to be used for many years due to their safety, low cost and adjuvanticity with different antigens. Two commonly used aluminum adjuvants, alumi... expand abstractnum hydroxide and aluminum phosphate have different adjuvanticity properties. Commercial recombinant protein hepatitis B vaccines containing aluminum hydroxide is facing low induction of immunity in some sections of the vaccinated population. OBJECTIVE: In this study, to follow the current global efforts in finding more potent hepatitis B vaccine formulations, adjuvanticity of aluminum phosphate, aluminum hydroxide and their combinations has been evaluated. METHODS: The formulated vaccines were administered intra-peritoneally (i.p.) to BALB/c mice and the titer of antibody was determined after 28 days using ELISA technique. The geometric mean of antibody titer (GMT, mIU/ml), seroconversion and seroprotection rates, ED50 (ng) and relative potency (microg/dose) of different formulations were determined. RESULTS: GMT of antibody titer, seroconversion and seroprotection rates showed significantly higher adjuvanticity for aluminum phosphate than other formulations. The ED50 of aluminum phosphate was approximately two fold less than other formulations. CONCLUSION: Aluminum phosphate showed more adjuvanticity than aluminum hydroxide and their combinations in hepatitis B protein vaccine. The use of aluminum phosphate as adjuvant leads to higher immunity which may result in more protective response in vaccinated groups. collapse abstract
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Chemical biology & drug design 2008 Aug; 72(3)
Exploring QSARs for antiviral activity of 4-alkylamino-6-(2-hydroxyethyl)-2-methylthiopyrimidines by support vector machine.
The support vector machine, which is a novel algorithm from the machine learning community, was used to develop quantitative structure activity relationship models to predict the antiviral activity of 4-alkylamino-6-(2-hydroxyethyl)-2-methylthiopyrim... expand abstractidines. The genetic algorithm was employed to select the variables that resulted in the best-fitted models. A comparison between the obtained results using support vector machine with those of multiple linear regression revealed that support vector machine model was much better than multiple linear regression. The root mean square errors of the training set and the test set for support vector machine model were calculated to be 0.102 and 0.205, and the correlation coefficients (r2) were 0.956 and 0.852, respectively. Furthermore, the obtained statistical parameter of leave-one-out (LOO) and leave-group-out (LGO) cross-validation test on support vector machine model were 0.893 and 0.881, respectively, which prove the reliability of this model. The results suggest that branching, volume and lipophilicity are the main independent factors contributing to the antiviral activities of the studied compounds. collapse abstract
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Chemical & pharmaceutical bulletin 2008 May; 56(6)
Electro-organic synthesis and characterization of new dihydroxybenzene dinitrile derivatives with fluorescent properties.
Novel fluorescent molecules were synthesized by designing an environmentally friendly method involving the bulk electrolysis technique. This electrochemical treatment process helps protect the environment by minimizing the toxic waste component of ef... expand abstractfluent. The electrochemical oxidation of 3,6-dihydroxybenzene-1,2-dinitrile (DBD) in the presence of benzenesulfinic acids was studied in an aqueous solution (H(2)O : AN, 90 : 10), which included an acetate buffer (pH=5.0). This research utilized a variety of experimental techniques, including cyclic voltammetry, controlled-potential electrolysis as well as spectroscopic identification of compounds produced as products. In addition, our fluorescent studies offered results in line with existing findings. At the wavelength of 205 nm, DBD and compound (6) were excited and their fluorescent emissions were monitored. collapse abstract
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Journal of drug targeting 2008 May; 16(5)
Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA-PEG-folate conjugate.
For folate-receptor-targeted anticancer therapy, docetaxel (DTX) nanoparticles (NPs) were produced employing polylactide-co-glycolide-polyethylene glycol-folate (PLGA-PEG-FOL) conjugate. The FOL-conjugated di-block copolymer was synthesized by coupli... expand abstractng the PLGA-PEG-NH(2) di-block copolymer with an activated folic acid. It was expected that FOL moieties were exposed on the micellar surface. The conjugates assisted in the formation of DTX NPs with an average size of 200 nm in diameter through an emulsification/solvent diffusion method. The FOL-targeted NPs showed a greater extent of intracellular uptake in FOL-receptor-positive cancer cells (SKOV3) in comparison with the non-targeted NPs, indicating that the FOL-receptor-mediated endocytosis mechanism could have a role in the cellular uptake of NPs. These results suggested that FOL-targeted DTX NPs could be a potentially useful delivery system for FOL-receptor-positive cancer cells. collapse abstract
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Pharmaceutical development and technology 13(1)
PLGA-PEG-PLGA tri-block copolymers as in situ gel-forming peptide delivery system: effect of formulation properties on peptide release.
Various controlled peptide and protein delivery systems have been investigated for their potential for treatment of chronic diseases. In situ gelling systems are very attractive due to their biocompatibility, biodegradability, and simple manufacturin... expand abstractg processes. The objective of this work was to investigate the effect of different excipients on release profile of calcitonin as a model protein from PLGA-PEG-PLGA thermally reversible gels. PLGA-PEG-PLGA with the ratio of PLGA to PEG equal to 2.5 was synthesized and characterized by (1)H NMR and gel permeation chromatography (GPC). The PLGA-PEG-PLGA polymeric solutions (25% w/w) containing calcitonin (0.05% w/w) and other excipients in various concentrations were prepared, and drug release from the thermally reversible gels was evaluated. It was shown that drug release from the systems was dramatically reduced when PEG 200 or PEG 1000 was added to the systems. This may be due to the effect of PEG as an internal cross-linking agent or the formation of PEG complexes that decrease the rate of drug release. Sodium laurel sulfate (SLS) was also shown to reduce the rate of drug release from the systems. This may be due to the large ionic heads of SLS that attract counterions of calcitonin. It can be concluded that the drug release rate from the systems can be controlled by using different excipients. collapse abstract
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Chemical biology & drug design 2008 Apr; 71(5)
A theoretical study on interactions between mitoxantrone as an anticancer drug and DNA: application in drug design.
This research is an effort to further understand the physicochemical interaction between the novel drug, mitoxantrone (MTX) and its biologic receptor, DNA. The ultimate goal is to design drugs that interact more with DNA. Understanding the physicoche... expand abstractmical properties of the drug as well as the mechanism by which it interacts with DNA, it should ultimately allow the rational design of novel anti-cancer or anti-viral drugs. Molecular modelling on the complex formed between MTX and DNA presented that this complex was indeed fully capable of participating in the formation of a stable intercalation site. Furthermore, the molecular geometries of MTX and the DNA bases (adenine, guanine, cytosine and thymine) were optimized with the aid of the B3LYP/6-31G* method. The properties of the isolated intercalator and its stacking interactions with the adenine...thymine (AT) and guanine...cytosine (GC) nucleic acid base pairs were studied with the DFTB method (density functional tight-binding), an approximate version of the DFT method, that was extended to cover the London dispersion energy. The B3LYP/6-31G* stabilization energies of the intercalator...base pair complexes were found 10.06 kcal/mol and 21.64 kcal/mol for AT...MTX and GC...MTX, respectively. It was concluded that the dispersion energy and the electrostatic interaction contributed to the stability of the intercalator.DNA base pair complexes. The results concluded from the comparison of the DFTB method and the Hartree-fock method point out that these methods show close results and support each other. collapse abstract
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Talanta 2008 Aug; 76(4)
Screening method for phthalate esters in water using liquid-phase microextraction based on the solidification of a floating organic microdrop combined with gas chromatography-mass spectrometry.
A simple and efficient liquid-phase microextraction (LPME) technique was developed using directly suspended organic microdrop coupled with gas chromatography-mass spectrometry (GC-MS), for the extraction and the determination of phthalate esters (dim... expand abstractethyl phthalate, diethyl phthalate, diallyl phthalate, di-n-butyl phthalate (DnBP), benzyl butyl phthalate (BBP), dicyclohexyl phthalate and di-2-ethylhexyl phthalate (DEHP)) in water samples. Microextraction efficiency factors, such as nature and volume of the organic solvent, temperature, salt effect, stirring rate and the extraction time were investigated and optimized. Under the optimized extraction conditions (extraction solvent: 1-dodecanol; extraction temperature: 60 degrees C; microdrop volume: 7 microL; stirring rate: 750 rpm, without salt addition and extraction time: 25 min), figures of merit of the proposed method were evaluated. The values of the detection limit were in the range of 0.02-0.05 microg L(-1), while the R.S.D.% value for the analysis of 5.0 microg L(-1) of the analytes was below 7.7% (n=4). A good linearity (r(2)>/=0.9940) and a broad linear range (0.05-100 microg L(-1)) were obtained. The method exhibited enrichment factor values ranging from 307 to 412. Finally, the designed method was successfully applied for the preconcentration and determination of the studied phthalate esters in different real water samples and satisfactory results were attained. collapse abstract
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