Improved synergic therapeutic effects of chemoradiation therapy with the aid of a co-drug-loaded nano-radiosensitizer under conventional-dose X-ray irradiation.

The goal of this work is to harness the advantages of a targeted hybrid nanostructure, BSA-coated Fe3O4 (F)-Au heterodimer, as a radiosensitizer and co-delivery vehicle of chemotherapeutic drugs for enhanced synergic cancer therapy and protection of healthy tissues. F-Au-BSA-MTX-CUR combines the abilities of enhanced X-ray radiation therapy (F-Au), long blood circulation time (BSA), tumor targeting (MTX), enhanced chemotherapy (MTX and CUR), and protection of normal cells against the harmful effects of radiation (CUR). In this work, we present the radioprotective and radiosensitizing effects of CUR on normal tissues and the tumor site, respectively. After technical evaluation, drug loading, drug release behavior, hemolysis assay, transfection efficacy, and cellular uptake studies with fluorescence microscopy, the biosafety and toxicity of the nanostructure was assessed in vitro and in vivo. Also, to confirm its power to improve synergistic chemoradiation therapy in mice, the antitumor effects of the designed treatment plan were assessed in a 4T1-tumor bearing mouse model. The in vivo antitumor effect evaluation interestingly reveals outstanding therapeutic power of the final formulation (F-Au-BSA-MTX-CUR) and further requirement of CUR as a radioprotective. This result importantly revealed the radioprotection effect of CUR. Co-delivery of the chemotherapeutic drugs MTX and CUR, combined with the radiosensitizing effect of the F-Au heterodimer and the radioprotective effect of CUR, showed promising prospects in cancer therapy.

Methotrexate anticancer drug delivery to breast cancer cell lines by iron oxide magnetic based nanocarrier.

In this study, we have achieved to provide an efficient method for production of iron oxide magnetic nanoparticles (MNPs) with arginine capping using in situ and one-pot co-precipitation method. As a novel drug delivery system, methotrexate (MTX) was conjugated to the obtained nanoparticles. These MNPs conjugate can potentially use in controlled drug delivery as carrier, and in magnetic resonance imaging as a contrast agent. Also, these nanoparticles can serve as a target in cancer therapy and diagnosis. These MNPs were covalently bond with MTX and can target the majority of cancer cells that their surfaces overexpressed by folate receptors. These conjugated nanoparticles were obtained through amide bond between the amine groups on their surface and the carboxylic acid end groups on MTX due to being functionalized with arginine. MTX was cleaved from nanoparticles according to drug release experiments in the presence of protease-like lysosomal conditions. Fe-Arg-MTX was characterized by transmission electron microscopes, dynamic light scattering, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. Furthermore, vibrating sample magnetometry analysis showed excellent magnetic properties of them. The average particle size of Fe-Arg-MTX was approximately 27 nm. The result revealed that the bare nanoparticles have no cytotoxicity against MCF-7, 4T1, and HFF-2 cell lines. Hemolysis assay showed that these nanoparticles are biocompatible. Regarding the research success, an efficient technique can be presented for drug delivery and controlled release and for studying cancer-fighting in alive creature's bodies.

New Insight about Biocompatibility and Biodegradability of Iron Oxide Magnetic Nanoparticles: Stereological and In Vivo MRI Monitor.

Iron oxide magnetic nanoparticles (IONPs) have attracted enormous attention because of their extensive medicinal and industrial applicability. PEGylated L-arginine modified iron oxide magnetic nanoparticles (PEG-Arg@IONPs) were synthesized and functioned in the present research as MRI contrast agents considered in vivo BALB/c model. The Synthesized PEG-Arg@IONPs were tracked in certain time intervals by MRI. The intensity of MR imaging of kidneys increased after administration of PEG-Arg@IONPs, which could confirm the emission of these nanoparticles by kidneys shortly after administration. Although PEG-Arg@IONPs were uptake by liver within 2 hours after injection, whereas, the signal change intensity of spleen, heart and kidneys confirmed that PEG-Arg@IONPs existed in other organs. The results illustrated that IONPs coated with PEGylated natural amino acid thin layers had a long circulation time and could be served as T2 contrast agents for diagnosis purpose. Notably, to the best of our knowledge, it was the first time the biocompatibility and biodegradability of IONPs was studied and evaluated by stereological and MRI technique.

Biotin-functionalized copolymeric PEG-PCL micelles for in vivo tumour-targeted delivery of artemisinin.

Artemisinin is used as an antimalarial and anticancer agent with minimal toxic effects on the host body. Biotin-PEG-PCL polymers have been used for targeted drug delivery to cancer, as well as to improve the pharmacokinetics of the drug and reduce its effects. In this study, biotin-conjugated copolymers were fabricated with polymerization of the ring opening method and the properties of copolymer and nanoparticles were investigated using various techniques. The toxicity of artemisinin and its nanoparticles have been investigated on MCF-7 and normal HFF2 cells. The results showed that the encapsulation efficacy of artemisinin in nanoparticles was 45.5 ± 0.41%. The release profile of the drug indicates that the release is slow and controlled and is approximately pH dependent. The results of artemisinin cell culture on human breast cancer cells showed that biotin-PEG-PCL nanoparticles had an inhibitory effect on MCF-7 cells and had no toxic effects on HFF2 cells. Anticancer activity in vivo in the 4T1 breast cancer model showed that tumour volumes were decreased up 40 mm3 by ART-loaded micelles and 76 mm3 by free ART, compared to the control group (2150 mm). In vivo results showed that this formulation significantly increases the accumulation of substances in the tumours. Therefore, the molecular formulation of ART-based copolymers can be a desirable process for cancer treatment purposes.

Antiplasmodial Property of Glycyrrhiza glabra Traditionally Used for Malaria in Iran: Promising Activity with High Selectivity Index for Malaria.

BACKGROUND: Development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents. The aim of this study was to assess antiplasmodial activity of the different fractions of root extract of Glycyrrhiza glabra. METHODS: Roots of G. glabra were collected from Tarom district of Zanjan Province in 2016 and then dried root material was chopped and consecutively extracted by the percolation method using solvents of different polarity. Resulting extracts were assessed for in vitro and in vivo anti-malarial and cell cytotoxicity activities. RESULTS: Among the three different solvent fractions studied, water-methanol and ethyl acetate fractions showed promising in vitro antiplasmodial activity against CQ-sensitive Plasmodium falciparum 3D7 strain (IC50= 9.95 and 13µg/ml, respectively). Further, the selectivity indices (HeLa cells versus P. falciparum) for the promising water-methanol fraction showed selectivity for P. falciparum and potential safer therapy for human. Interestingly, water-methanol and ethyl acetate fractions showed a significant suppression of parasite growth (72.2% and 65%, respectively) in comparison with control group in mice infected with P. berghei (P< 0.05). CONCLUSION: The promising antiplasmodial activity of the aqueous fraction of G. glabra obtained in our study warrant bioassay-guided fractionation of this fraction to identify active principles responsible for antiplasmodial activity.

Preparation, characterization and in vitro anticancer activity of paclitaxel conjugated magnetic nanoparticles.

In this study, magnetic nanoparticles (MNPs) coated with L-aspartic acid (F-Asp NPs) were synthesized through a co-precipitation method and conjugated with paclitaxel (PTX) (F-Asp-PTX NPs) by esterification reaction between the carboxylic acid end groups on MNPs surface and the hydroxyl groups of the PTX and studied its cytotoxic effect in vitro. The successful conjugating of PTX onto the nanoparticles (NPs) was confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) techniques. The results showed that the average size was 46.11 ± 7.8 (mean ± SD (n = 25)) nm. The cytotoxicity of void of PTX and F-Asp-PTX NPs were compared to each other by MTT assay of the treated MCF-7 cell line. The F-Asp-PTX NPs showed pH-dependent drug release behavior. These studies specify that F-Asp-PTX NPs have a very remarkable anticancer effect, for breast cancer cell line.

Co -delivery of Sulforaphane and Curcumin with PEGylated Iron Oxide-Gold Core Shell Nanoparticles for Delivery to Breast Cancer Cell Line.

Co-delivery approach has been recommended to reduce the amount of each drug and to achieve the synergistic effect for cancer treatment. Curcumin (CUR) and sulforaphane (SF) have antitumor effects, but their application is limited because of their low water solubility and poor oral bioavailability. To improve the bioavailability and solubility of SF and CUR, we performed an innovative co-delivery of them with PEGylated gold coated Fe3O4 magnetic nanoparticles (PEGylated Fe3O4@Au NPs) to endorse SF and CUR maintenance as an effective and promising antitumor drugs. The structure of the synthesized nanocarriers evaluated by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, vibrating sample magnetometer, dynamic light scattering and Fourier transform infrared spectroscopy. The results revealed that the zeta potential of CUR and SF-loaded NPs were about -15.4 mV and the average sizes were 80.57 nm. They were monodispersed (polydispersity index = 0.161 ± 0.016) in water with high drug-loading capacity and stability. CUR and SF were encapsulated into NPs with loading capacity of 17.32 ± 0.023% and 16.74 ± 0.015% and the entrapment efficiency of 83.72 ± 0.14% and 81.20 ± 0.18% respectively. The in-vitro study of SF and CUR loaded PEGylated Fe3O4@Au NPs on human breast adenocarcinoma cell line (MCF-7) confirmed that cytotoxicity of SF and CUR can enhance when they are loaded on PEGylated Fe3O4@Au NPs in comparison to free SF and CUR. The results of real-time PCR and flow cytometry shown that this combination can increase therapeutic effects of SF and CUR by apoptosis and necrosis induction as well as inhibiting of migration in MCF-7 cell line.

Theranostic nanoparticles based on magnetic nanoparticles: design, preparation, characterization, and evaluation as novel anticancer drug carrier and MRI contrast agent.

In this work, we reported the synthesis of curcumin (CUR)-loaded hydrophilic and hydrophobic natural amino acids (AAs)-modified iron oxide magnetic nanoparticles (IONPs). Two types of AAs, l-lysine (Lys) and l-phenylalanine (PhA), were selected to study their effects on loading capacity, release profile of CUR, biocompatibility, and anticancer activity. CUR-loaded AAs-modified IONPs (F@AAs@CUR NPs) were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. Next, the various kinetic equations were fitted to the release data of CUR from F@Lys@CUR NPs and F@PhA@CUR NPs. Additionally, hemolysis test and MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AAs-coated IONPs. Finally, the anticancer activity of F@AAs@CUR NPs examined on MCF-7 breast cancer cell line. The results indicate that these nanocarriers are nontoxic and biocompatible and also F@AAs@CUR NPs are suitable carriers for delivery of curcumin and even other hydrophobic drugs. Also, the MRI training established the effectiveness of IONPs as contrast agent for the revealing of tumor as evidenced from the phantom images as well as higher T2 relaxivity.

Production of biological nanoparticles from bovine serum albumin as controlled release carrier for curcumin delivery.

This study described a curcumin (CUR) loaded bovine serum albumin nanoparticles (BSA@CUR NPs), which could solubilize the poorly water-soluble drug and increase the therapeutic efficacy of the drug. BSA@CUR NPs were synthesized by a simple coacervation procedure. The resultant BSA@CUR NPs showed a spherical shape, with a diameter of 92.59±16.75nm (mean ± SD) nm and a ζ-potential of - 9.19mV. The in vitro drug release study of CUR showed a sustained and controlled release pattern. Cellular toxicity of BSA NPs was also investigated on HFF2 cell lines. Additionally, a hemolysis test of as prepared NPs were performed for investigation of hemocompatibility. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. The in vitro anticancer activity of the BSA@CUR NPs were performed by MTT assay on MCF-7 cancer cells. These results suggest that BSA@CUR NPs are a new drug delivery system for cancer therapy.

Enzymatic stimuli-responsive methotrexate-conjugated magnetic nanoparticles for target delivery to breast cancer cells and release study in lysosomal condition.

In this study, magnetic nanoparticles (MNPs) coated with glycine (F-Gly NPs) and conjugated with methotrexate (MTX) (F-Gly-MTX NPs) were synthesized through a coprecipitation method followed by amidation reaction between the carboxylic acid end groups on MTX and the amine groups on the MNPs surface and studied its cytotoxic effect in vitro. The successful conjugating of MTX onto the nanoparticles (NPs) was confirmed by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. The results showed that the average size was 46.82 ± 5.03 nm. This target drug delivery system is dependent on the release of the MTX within the lysosomal compartment. Hemolysis assay and cytotoxicity study results on HFF-2 and HEK-293 cell lines show that as prepared MNPs are biocompatible. The cytotoxicity of void of the MTX and F-Gly-MTX NPs were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of the treated MCF-7 cell line. Enzymatic release studies exhibited the release of the MTX via peptide bond cleavage in the presence of proteinase K. These studies specify that the F-Gly-MTX NPs have a very remarkable anticancer effect, for breast cancer cell line. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1646-1654, 2018.

Bovine Serum Albumin (BSA) coated iron oxide magnetic nanoparticles as biocompatible carriers for curcumin-anticancer drug.

The bovine serum albumin-coated magnetic nanoparticles (F@BSA NPs) were prepared as curcumin (CUR) carriers through desolvation and chemical co-precipitation process. The characteristics of CUR loaded F@BSA NPs (F@BSA@CUR NPs) were determined by X-ray diffraction (XRD), thermogravimetric analysis (TGA), fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and vibrating-sampling magnetometry (VSM) techniques. It was found that the synthesized F@BSA@CUR NPs were spherical in shape with an average size of 56 ±â€¯11.43 nm (mean ± SD (n = 33)), ζ-potential of -10.1 mV, and good magnetic responsivity. Meanwhile, the drug content of the nanoparticles was 6.88%. These F@BSA@CUR NPs also demonstrated sustained release of CUR at 37 °C in different buffer solutions. Cellular toxicity of F@BSA@CUR NPs was studied on HFF2 cell line. Also, the cytotoxicity of F@BSA@CUR NPs towards MCF-7 breast cancer cells was investigated. The results revealed that F@BSA@CUR NPs have significant cytotoxicity activity on MCF-7 cell line.

Preparation and in vivo evaluation of anti-plasmodial properties of artemisinin-loaded PCL-PEG-PCL nanoparticles.

PURPOSE: Artemisinin (ART) has anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and anti-malarial effects, but its application is limited due to its low water solubility and poor oral bioavailability. In this study, the bioavailability, water solubility, and anti-plasmodial property of ART were improved by PCL-PEG-PCL tri-block copolymers. METHODS: The structure of the copolymers was characterized by 1H NMR, FT-IR, DSC, and GPC techniques. ART was encapsulated within micelles by a single-step nano-precipitation method, leading to the formation of ART-loaded PCL-PEG-PCL micelles. The obtained micelles were characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). The in vivo anti-plasmodial activity of ART-loaded micelles was measured against Plasmodium berghei infected Swiss albino mice. RESULTS: The results showed that the zeta potential of ART-loaded micelles was about -8.37 mV and the average size was 91.87 nm. ART was encapsulated into PCL-PEG-PCL micelles with a loading capacity of 19.33 ± 0.015% and encapsulation efficacy of 87.21 ± 3.32%. In vivo anti-plasmodial results against P. berghei showed that multiple injections of ART-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of ART. CONCLUSION: These results suggested that PCL-PEG-PCL micelles would be a potential carrier for ART for the treatment of malaria.

Niosome: A Promising Nanocarrier for Natural Drug Delivery through Blood-Brain Barrier.

Niosomes (the nonionic surfactant vesicles), considered as novel drug delivery systems, can improve the solubility and stability of natural pharmaceutical molecules. They are established to provide targeting and controlled release of natural pharmaceutical compounds. Many factors can influence on niosome construction such as the preparation method, type and amount of surfactant, drug entrapment, temperature of lipids hydration, and the packing factor. The present review discusses about the most important features of niosomes such as their diverse structures, the different preparation approaches, characterization techniques, factors that affect their stability, their use by various routes of administration, their therapeutic applications in comparison with natural drugs, and specially the brain targeting with niosomes-ligand conjugation. It also provides recent data about the various types of ligand agents which make available active targeting drug delivery to the central neuron system. This system has an optimistic upcoming in pharmaceutical uses, mostly with the improving availability of innovative schemes to overcome blood-brain barrier and targeting the niosomes to the brain.

Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL-PEG-PCL copolymeric-based micelles.

A reliable and efficient drug delivery system using PCL-PEG-PCL copolymers was established for the anti-cancer compound sulforaphane (SF) in this study. Encapsulated SF by PCL-PEG-PCL nanoparticles led to formation of SF-loaded PCL-PEG-PCL micelles. Micelles characterization and stability, the particle size and their morphology were determined by DLS and AFM. The loading efficiency of SF was 19.33 ± 1.28%. The results of AFM showed that the micelles had spherical shapes with the size of 107 nm. In vitro release of SF from SF-entrapped micelles was remarkably sustained. The cytotoxicity of free SF, PCL-PEG-PCL and SF/PCL-PEG-PCL micelles was analysis by MTT colorimetric assay on MCF-7, 4T1 and MCF10A cell lines. Expression levels of BCL-2, PARP, COX-2, Caspase-9 and ACTB genes were quantified by real-time PCR. Flow cytometry analysis was performed using the Annexin V-FITC Apoptosis Detection Kit to evaluate the apoptotic effects of free SF compared with SF/PCL-PEG-PCL micelles. Study of the in vivo pharmacokinetics of the SF-loaded micelles was carried out on SF-loaded PCL-PEG-PCL micelles in comparison with free SF. The results of in vivo experiments indicated that the SF loaded micelles significantly reduced the tumor size. In vivo results showed that the multiple injections of SF-loaded micelles could prolong the circulation period and increase the therapeutic efficacy of SF. Also, in comparison with the free-SF solution, encapsulation of the SF in micelles increased the mean residence time from 0.5 to 4 h and the area under the concentration-time curve up to 50 folds.

Sulforaphane delivery using mPEG-PCL co-polymer nanoparticles to breast cancer cells.

PURPOSE: Among the potent anticancer agents, d,l-sulforaphane (SF) is very effective against many different types of cancer cells. Its clinical application is restricted because of its hydrophobicity, low gastrointestinal absorption and poor bioavailability. In the present study, a reliable micellar delivery system using monomethoxypoly (ethylene glycol)-poly (ɛ-caprolactone) (mPEG-PCL) was established. The encapsulation of SF inside mPEG-PCL as a nano-carrier was established and the cytotoxicity assay against human breast cancer cell line was evaluated. METHODS: In this study, SF was encapsulated within mPEG-PCL micelles through a single-step nano-precipitation method, leading to creation of SF-loaded mPEG-PCL (SF/mPEG-PCL) micelles. Di-block mPEG-PCL copolymers were synthesized and used to prepare micelles. MPEG-PCL copolymer was characterized by HNMR, FTIR, differential scanning calorimetry and gel permeation chromatography techniques. Characterization, stability of micelles, the particle size and morphology were determined. The release profile of the SF from the micelles which prepared by the drug-loaded copolymer, was evaluated. The cytotoxicity of free SF, mPEG-PCL and SF-loaded mPEG-PCL micelles was compared with each other by performing MTT assay of the treated MCF-7 cell line. Expression levels of BCL-2, MMP-9, BCL-XL, BAK, BAX and GAPDH (endogenous gene) as control were quantified by real time PCR. To evaluate the apoptotic effects of Free SF compared with SF-loaded mPEG-PCL micelles, flow cytometry analysis was done using the annexin V-FITC apoptosis detection kit. RESULTS: Our studies resulted in a successful establishment of uniformity and spherical SF-loaded mPEG-PCL micelles. The encapsulation efficiency of SF was 86 ± 1.58%. The results of atomic force microscopy revealed that the micelles have spherical shapes with size of 107 nm. In vitro release of SF from SF-entrapped micelles was remarkably sustained. The mPEG-PCL micelle showed little cytotoxicity in the case of MCF-7 cell line with concentration up to 1.5 mg/ml, whereas the SF-loaded mPEG-PCL micelles at all concentrations significantly was cytotoxic in the case of MCF-7 cell line. Finally, real-time PCR and flow cytometry were used to demonstrate that the SF-loaded mPEG-PCL could be efficiently inducing apoptosis in MCF-7 cell line. CONCLUSION: We achieved to a successful formulation of SF-loaded m-PEG/PCL micelles in this study. Based on the cytotoxicity results of mPEG-PCL micelles against human breast cancer cell line (MCF-7) in this study, it suggested that SF/mPEG-PCL micelles can be an effective breast cancer treatment strategy in the future.

Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles.

Curcumin (CUR) has been associated with anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability. To progress the bioavailability and water solubility of CUR, we synthesized five series of mono methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by H NMR, FTIR, DSC and GPC techniques. In this study, CUR was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of CUR-loaded mPEG-PCL (CUR/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxicity of void CUR, mPEG-PCL and CUR/mPEG-PCL micelles was compared to each other by performing MTT assay of the treated MCF-7 and 4T1 cell line. Study of the in vivo pharmacokinetics of the CUR-loaded micelles was also carried out on selected copolymers in comparison with CUR solution formulations. The results showed that the zeta potential of CUR-loaded micelles was about -11.5mV and the average size was 81.0nm. CUR was encapsulated into mPEG-PCL micelles with loading capacity of 20.65±0.015% and entrapment efficiency of 89.32±0.34%. The plasma AUC (0-t), t1/2 and Cmax of CUR micelles were increased by 52.8, 4.63 and 7.51-fold compared to the CUR solution, respectively. In vivo results showed that multiple injections of CUR-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of CUR. These results suggested that mPEG-PCL micelles would be a potential carrier for CUR.

Development of a High-Resolution Melting Analysis Method for CYP2C19*17 Genotyping in Healthy Volunteers.

BACKGROUND: Genetic polymorphisms of drug metabolisms by cytochrome P450 (P450s) could affect drug response, attracting particular interest in the pharmacogenetics. Due to the importance of CYP2C19* 17 allele and its capability of super- fast metabolism and also lack of information about distribution of the alleles in Iranian population, this research aimed to use High Resolution Melting (HRM) method compared to PCR-RFLP for genotyping healthy Iranian population. METHODS: Blood samples were collected from 100 healthy Iranian volunteers. DNA was extracted by salting out method. Real-time PCR was used for amplification of the CYP2C19 gene and the alleles were identified by HRM. Sequencing was used to confirm the amplified DNA fragments and data were analyzed using SPSS software ver.18. RESULTS: The frequency of alleles CYP2C19*1/*1, CYP2C19*1/*17 and CYP2C19*17/*17 were estimated as 58.33, 29.1 and 11.1%, respectively. Specificity and sensitivity of HRM method were 90% and 100%, with respect to PCR-RFLP. Also, HRM analysis has been evaluated as a faster and more effective approach. CONCLUSION: Comparison of our results based on HRM analysis with PCR-RFLP showed that our developed method is rapid, accurate, fast and economic to study the CYP2C19*17 allele and it is appropriate for other similar population genetic studies.

D, L-Sulforaphane Loaded Fe3O4@ Gold Core Shell Nanoparticles: A Potential Sulforaphane Delivery System.

A novel design of gold-coated iron oxide nanoparticles was fabricated as a potential delivery system to improve the efficiency and stability of d, l-sulforaphane as an anticancer drug. To this purpose, the surface of gold-coated iron oxide nanoparticles was modified for sulforaphane delivery via furnishing its surface with thiolated polyethylene glycol-folic acid and thiolated polyethylene glycol-FITC. The synthesized nanoparticles were characterized by different techniques such as FTIR, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, scanning and transmission electron microscopy. The average diameters of the synthesized nanoparticles before and after sulforaphane loading were obtained ∼ 33 nm and ∼ 38 nm, respectively, when ∼ 2.8 mmol/g of sulforaphane was loaded. The result of cell viability assay which was confirmed by apoptosis assay on the human breast cancer cells (MCF-7 line) as a model of in vitro-cancerous cells, proved that the bare nanoparticles showed little inherent cytotoxicity, whereas the sulforaphane-loaded nanoparticles were cytotoxic. The expression rate of the anti-apoptotic genes (bcl-2 and bcl-xL), and the pro-apoptotic genes (bax and bak) were quantified, and it was found that the expression rate of bcl-2 and bcl-xL genes significantly were decreased when MCF-7 cells were incubated by sulforaphane-loaded nanoparticles. The sulforaphane-loaded into the designed gold-coated iron oxide nanoparticles, acceptably induced apoptosis in MCF-7 cells.

Curcumin-loaded guanidine functionalized PEGylated I3ad mesoporous silica nanoparticles KIT-6: practical strategy for the breast cancer therapy.

In this research, we have synthesized guanidine functionalized PEGylated mesoporous silica nanoparticles as a novel and efficient drug delivery system (DDS). For this purpose, guanidine functionalized PEGylated I3ad mesoporous silica nanoparticle KIT-6 [Gu@PEGylated KIT-6] was utilized as a promising system for the effective delivery of curcumin into the breast cancer cells. The modified mesoporous silica nanoparticles (MSNs) was fully characterized by different techniques such as transmission and scanning electron microscopy (TEM & SEM), N2 adsorption-desorption measurement, thermal gravimetric analysis (TGA), X-ray powder diffraction (XRD), and dynamic light scattering (DLS). The average particle size of [Gu@PEGylated KIT-6] and curcumin loaded [Gu@PEGylated KIT-6] nanoparticles were about 60 and 70 nm, respectively. This new system exhibited high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. It showed pH-responsive controlled characteristics and highly programmed release of curcumin leading to the satisfactory results in in vitro breast cancer therapy. Our results depicted that the pure nanoparticles have no cytotoxicity against human breast adenocarcinoma cells (MCF-7), mouse breast cancer cells (4T1), and human mammary epithelial cells (MCF10A).

Anti-leishmanial and toxicity activities of some selected Iranian medicinal plants.

Leishmaniasis is caused by protozoan parasites belonging to the genus Leishmania. Cutaneous leishmaniasis is the most common form of leishmaniasis in Iran. As there is not any vaccine for leishmaniasis, treatment is important to prevent the spreading of parasites. There is, therefore, a need to develop newer drugs from different sources. The aim of this study was to assess anti-leishmanial activity of the ethanolic extracts of 17 different medicinal plants against Leishmania major promastigotes and macrophage cell line J774. The selection of the hereby studied 17 plants was based on the existing information on their local ethnobotanic history. Plants were dried, powdered, and macerated in a hydroalcoholic solution. Resulting extracts have been assessed for in vitro anti-leishmanial and brine shrimp toxicity activities. Four plants, Caesalpinia gilliesii, Satureia hortensis, Carum copticum heirm, and Thymus migricus, displayed high anti-leishmanial activity (IC50, 9.76 ± 1.27, 15.625 ± 3.76, 15.625 ± 5.46, and 31.25 ± 15.44 µM, respectively) and were toxic against the J774 macrophage cell line at higher concentrations than those needed to inhibit the parasite cell growth (IC50, 45.13 ± 3.17, 100.44 ± 17.48, 43.76 ± 0.78, and 39.67 ± 3.29 µM, respectively). Glucantime as positive control inhibited the growth of L. major promastigotes with IC50 = 254 µg/ml on promastigotes (1 × 10(6)/100 µ/well) of a log phase culture, without affecting the growth of J774 macrophages. These data revealed that C. gilliesii, S. hortensis, C. copticum heirm, and T. migricus extracts contain active compounds, which could serve as alternative agents in the control of cutaneous leishmaniasis. The activity of these herbs against L. major promastigotes and macrophage cell line J774 was reported for the first time in our study.