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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. [ABSTRACT FROM AUTHOR]

In this project, TiO@ZnO nanoparticles core-shell nanostructured and titanium dioxide@ mesoporous zinc oxide-graphene oxide (TiO@ZnO-GO) hybrid nanocomposites as controlled targeted drug delivery systems were synthesized by a facile sono-chemical method. We prepared a novel mesoporous and core-shell structure as a drug nanocarrier (NCs) for the loading and pH-responsive characteristics of the chemotherapeutic curcumin. The structure, surface charge, and surface morphology of NCs were studied using with X-ray diffraction, Fourier transform infrared spectroscopy, dynamic light scattering, brunauer-emmett-teller, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The SEM and TEM images of NCs show the uniform hexagonal mesoporous morphology with average grain size of about ∼ 190 nm. The drug loading was very high about 16 and 19 for TiO@ZnO and TiO@ZnO-GO, respectively. The NCs showed pH-dependent drug release behavior. Drug release from TiO@ZnO-GO in neutral pH were higher than in acidic medium, due to anionic charge of GO nanosheet. MTT assay results showed that the curcumin-loaded NCs showed significant toxicity due to which cell viability reduced to below 50% at 140 μg/mL concentration, thereby confirming its anticancer effects. The goal of this study is the application of water-dispersed TiO@ZnO-GO with pH-dependent release properties for design a new drug delivery carrier. [ABSTRACT FROM AUTHOR]

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 vitrorelease 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Fe 3 O 4 magnetic nanoparticles (PEGylated Fe 3 O 4 @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 Fe 3 O 4 @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 Fe 3 O 4 @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.

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.