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In this article, Fe3O4/GO and Fe3O4/ZnO/GO nanocomposites (NPs) synthesized by thermal treatment at 823 K, and their drug delivery properties for curcumin (CUR) as an anticancer drug were investigated. The structural, morphological, and magnetic properties of these Nps were studied. The results of XRD, FTIR and EDX analyses indicated the synthesis of pure and crystalline structures of GO, Fe3O4/GO and Fe3O4/ZnO/GO NPs. Moreover, the mean size of spherical shape in Fe3O4/GO and Fe3O4/ZnO/GO nanoparticles was 42.36 and 53.21 nm, respectively. Based on the results of release and loading at different pHs, the drug is well loaded on the NPs and released at the tumor site. Based on these studies, the drug loading percentage on Fe3O4/GO is higher than Fe3O4/ZnO/GO. Also, the results showed that 41.65% of the drug is released from Fe3O4/GO and 23.43% from Fe3O4/ZnO/GO in the first ten hours after being in the cancer cell site. The Hemolysis test of prepared NPs and the cytotoxicity of NCs and CUR-loaded on NCs against U87 cancer cells and fibroblast human cells were investigated using the MTT assay. The toxic effect of Fe3O4/GO and of Fe3O4/ZnO/GO was more in U87 cancer cells compared to normal fibroblast cells. The results of anticancer activity of Nano-carriers on brain cancer cell lines revealed that CUR-loaded nanocrystals (NCs) have significant cytotoxicity activity on U87. Therefore, these NCs are capable of acting as drug delivery systems for anti-cancer drugs like CUR. [ABSTRACT FROM AUTHOR]

In this project, Calcium ferrite/polyvinyl alcohol (CaFe2O4@PVA) nanocarriers were prepared by a thermal-treatment method at three different temperatures (773, 823 and 923 K). The nanocarriers were used as drug delivery systems (DDS) to deliver curcumin (CUR) and were utilized as a new structure for photo dynamic therapy (PDT). Drug loading and release study of CUR were performed and it was observed that nanocarriers showed a pH dependent drug release behavior. MTT assay, Hemolysis assay and lethal dose test were applied to determine the cytotoxicity of nanocarriers. These tests indicated that synthesized nanocarriers can be considered as nontoxic. Also, the photodynamic therapy experiments were performed by two groups: one group of cells were treated by different concentrations of nanocarriers without light and the other group were exposed to light. Then, the efficacy of PDT was determined by MTT and it was revealed that whenever nanocarriers were exposed to light the cytotoxicity was significantly high. Therefore, it was revealed that these nanocarriers are suitable to be utilized as a drug delivery systems and photo dynamic therapy agent. [ABSTRACT FROM AUTHOR]

In The present project, a variety of MnFe2O4 (Mn) and Cr2Fe6O12 (Cr)-based nanocarriers (NCs) were synthesized as photosensitizer and NCs for delivery of chemotherapeutic curcumin (CUR) and provide a new structure for Photodynamic Therapy (PDT). For determining efficiency of NCs release study, MTT assay, lethal dose test and hemolysis assay were carried out. The release study showed the release of CUR from NCs was pH-dependent, but, every NCs had its own behavior for releasing the drug. The data acquired from the release study showed the CUR release from Mn can reach to over 90% at acidic media instead of 41% at neutral media. However, the CUR released from Cr were approximately equal as Cr had equal zeta potential at both media. Hemolysis activity and lethal dose test displayed the cytotoxicity of NCs was neglectable at both in vitro and in vivo study. Also, the results of anti-cancer activity assay (MTT assay) showed that both of Cr and Mn NCs are suitable systems for PDT. Therefore, the results demonstrated that Mn is suitable NCs for PDT and anticancer drugs delivery of therapeutic drugs. [ABSTRACT FROM AUTHOR]

High atomic number Z, nanoparticles are able to enhance the photoelectric and Compton effects under X-Ray irradiation resulting the increase of radiation therapy efficacy. To achieve enhanced radiation therapy, Bi2S3 biocompatible particles coated with bovine serum albumin (BSA) (Bi2S3@BSA HNPs) were prepared through a BSA-mediated biomineralization procedure under green conditions. Then, to achieve improved chemo-radiation therapy against HT-29 cancer cells, curcumin (CUR) as natural anti-cancer therapy agent loaded on the Bi2S3@BSA (Bi2S3@BSA@CUR HNPs). Next, this synthesized nanodrug was evaluated for physical and chemical properties and in vitro cytotoxicity studies. Here, in vitro enhanced chemo-radiation combination therapy power was evaluated against HT-29 cell line under 2 Gy and 6 Gy X-ray irradiation doses. The Bi2S3@BSA HNPs without irradiation rarely affect cell viability which shown the non-toxicity of Bi2S3@BSA HNPs. The result of this study proved that Bi2S3@BSA@CUR HNPs can be used as both proficient vehicles for effective delivery of CUR and radiosensitizer in the treatment of cancer. In addition, the result of this study confirmed that the combination of high Z-element nanoradiosensitizer, Bi2S3@BSA HNPs, with a natural anti-cancer drug, CUR, enhanced therapeutic power against HT-29 cells. [ABSTRACT FROM AUTHOR]

In this study, we synthesized methoxy poly(ethylene glycol)-poly(ε-caprolactone) diblock copolymers as water soluble nanocarriers to investigate the in vivo anti-inflammatory characteristic of rosuvastatin-loaded nanocarriers. For determining the structure of prepared nanocarriers, we used proton nuclear magnetic resonance, gel permeation chromatography, Fourier-transform infrared spectroscopy, atomic force microscopy, and dynamic scanning calorimetry method. Nano-precipitation method was used for loading of rosuvastatin into copolymeric nanocarriers. The goal of this study is investigation of the anti-inflammatory effects of rosuvastatin-loaded nanocarriers in comparison with indomethacin. The paw edema thickness was measured during 4 h after gavage of nanocarriers in acute inflammation-induced rats, and the ability of nanocarriers to inhibit the edema was calculated. Rosuvastatin was loaded in nanocarriers with a loading capacity of 9.38 ± 0.96% and an encapsulation efficiency of 62.50 ± 0.84%; moreover, rosuvastatin and rosuvastatin nanocarriers displayed considerable anti-inflammatory activity in this study. This study indicated that rosuvastatin and rosuvastatin nanocarriers have anti-inflammatory characteristic and we can conclude that in addition to lipid lowering affect, statins have potential for anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Purpose: In this study, methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG–PCL) di-block copolymers were synthesized. The purpose of this work is to investigate the in vivo anti-inflammatory effects of simvastatin-loaded micelles. Methods: The structure of synthesized copolymers was characterized by using HNMR, FTIR, and GPC techniques. Simvastatin was encapsulated in micelles through a single-step nano-precipitation method, leading to the formation of simvastatin-loaded mPEG–PCL (simvastatin-mPEG–PCL) micelles. In this study, the anti-inflammatory effects of simvastatin/mPEG–PCL micelles versus indomethacin were investigated in acute inflammation-induced rats. The paw edema thickness was measured 1, 2, 3, and 4 h after injection of formulation. The inhibition of edema in various groups were calculated and reported by percentages. Results: The results showed that the zeta potential of micelles was about −14.9 ± 0.47 mV and the average size was in range of 66.10 ± 0.34 nm. Simvastatin was encapsulated in mPEG–PCL micelles with a loading capacity of 9.63 ± 0.87% and an encapsulation efficiency of 64.20 ± 0.79%. Simvastatin and simvastatin-mPEG–PCL micelles showed significant anti-inflammatory activity in the present study. Conclusions: This study revealed that simvastatin and simvastatin/mPEG–PCL micelles both have anti-inflammatory effects and suggested that statins have potential anti-inflammatory activity along with their lipid lowering properties. [ABSTRACT FROM AUTHOR]

In this study, we designed a polymersome system for the controlled release of methotrexate (MTX) as an anticancer drug with the objective of improving the loading efficiency of the drug in polymersomes as well as achievement of an efficient control on the release rate of drug from nanocarriers. We synthesized mono methoxy poly(ethylene glycol)-poly(e-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) techniques. MTX was encapsulated within nanoparticles (NPs) through multiple emulsion method. The resulting NPs were characterized further by various techniques such as atomic force microscopy (AFM) and dynamic light scattering (DLS). Next, the various kinetic equations were fitted to the release data of MTX from MTX-loaded mPEG-PCL polymersomes. The results showed that the zeta potential of MTX-loaded mPEG-PCL polymersomes was about -5.49 mV and the average size was 49.18 nm. MTX was encapsulated into polymersomes loading capacity of 12 ± 0.09% and encapsulation efficiency of 45.5 ± 0.41%. The metabolic activity assays of void of MTX, mPEG-PCL polymersomes, and MTX-loaded mPEG-PCL polymersomes were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of the treated MCF-7 cell lines. It can be concluded that application of NPs is a better and more effective strategy for controlled and slow release of MTX in the treatment of cancer. [ABSTRACT FROM AUTHOR]

This study is a report about the synthesis iron oxide magnetic nanoparticles (IONPs) which modified with positive and negative charged amino acids (AAs). L-Arginine (Arg) and L-aspartic acid (Asp) which have of guanidinium and carboxylic acid groups, respectively, were selected for this study. After loading chrysin in amino acids modified iron oxide magnetic nanoparticles (F@AAs@Chrysin NPs), it was characterized by XRD, TGA, FTIR, VSM, and TEM techniques. Finally, MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AA coated IONPs. The results show that, the ζ-potential and average size of F@Arg@chrysin NPs and F@Asp@chrysin NPs were to −3.87, −2.12 mV, 18.75 ± 2.40 (mean ± SD (n = 50)) nm, and 19.86 ± 2.22 (mean ± SD (n = 48)) nm, respectively. Also, the results indicated that these F@AAs@Chrysin NPs were appropriate for delivery of chrysin. Furthermore, the phantom MRI studies showed the IONPs can be used as contrast agent for the revealing of tumor. [ABSTRACT FROM AUTHOR]

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 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. [ABSTRACT FROM AUTHOR]

Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone with anticancer properties, but its application is limited because of its low water solubility. To increase the bioavailability and water solubility of ART, we synthesized three series of poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) (PCL-PEG-PCL) tri-block copolymers. The structure of the copolymers was characterized by HNMR, FTIR, DSC and GPC techniques. ART was encapsulated inside micelles by a nanoprecipitation method which leading to the formation of ART/PCL-PEG-PCL micelles. The obtained micelles were characterized by DLS and AFM technique. The results showed that the average size of micelles was about 83.22 nm. ART was encapsulated into PCL-PEG-PCL micelles with encapsulation efficacy of 89.23 ± 1.41%. In vivo results demonstrated that this formulation significantly increased drug accumulation in tumours. Pharmacokinetic study in rats revealed that in vivo drug exposure of ART was significantly increased and prolonged by intravenously administering ART-loaded micelles when compared with the same dose of free ART. The MTT assay showed that bare PCL-PEG-PCL micelles is non-toxic to MCF7 and 4T1 cancer cell lines whereas the ART/PCL-PEG-PCL micelles showed a specific toxicity to both cancer cell lines. Therefore, the polymeric micellar formulation of ART based copolymer could provide a desirable process for ART delivery. [ABSTRACT FROM AUTHOR]

Denderimer-modified magnetic nanoparticles are a promising drug delivery nanosystem which can improve the therapeutic efficacy of chemotherapy drugs and can also be beneficial as magnetic resonance (MR) images contrast agent. The present study introduces the preparation and characterization of the potential therapeutic efficiency of curcumin (CUR)-loaded denderimer-modified citric acid coated Fe3O4 NPs. Polyamidoamine (PAMAM, generation G5) was used to encapsulate citric acid coated Fe3O4 nanoparticles. The successful preparation of CUR-loaded nanocarriers were confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. The loading capacity and encapsulation efficiency of CUR molecules were 12 ± 0.03% and 45.58 ± 0.41%, respectively. The anticancer effect of void CUR and CUR-loaded nanocarriers were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on treated MCF-7 cell line. It can be concluded that application of nanoparticles can be more effective strategy for controlled and slow release of CUR in human breast cancer treatment. [ABSTRACT FROM AUTHOR]

Miktoarm star copolymers are relatively considered to be a new and unique class of macromolecules, and are a new topical area due to the unique properties by varying their polymer arms. This macromolecules with the AmBn architecture, have m arms of polymer A and n arms of polymer B connected at one central junction point. Over the past decade, miktoarms have been used in biomedical applications such as drug delivery, gene delivery, tissue engineering, diagnosis, and antibacterial/antifouling biomaterials. The intensified interest in miktoarms is attributed to their unique topological structures and attractive physical/chemical properties, including low critical micelle concentration (CMC) in solutions, encapsulation capability, internal and peripheral functionality, and enhanced stimuli-responsiveness. This review outlines the advances in the use of miktoarms in drug delivery for their good performance in biocompatibility, biodegradability and sustained, controlled and targeted drug delivery during the past decade and some unique self-assembly behaviors of miktoarm star copolymers have been reported. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX), a stoichiometric inhibitor of dihydrofolate reductase enzyme, is a chemotherapeutic agent for treating a diversity of neoplasms. In this study, we design and developed a new formulation of MTX that serves as drug carrier and examined its cytotoxic effect in vitro. This target drug delivery system is dependent on the release of the MTX within the lysosomal compartment. The iron oxide magnetic nanoparticles (IONPs) were first surface-coated with L-lysine and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the IONPs surface. MTX-conjugated L-lysine coated IONPs (F-Lys-MTX NPs) was characterized by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. The cytotoxicity of the void of MTX and F-Lys-MTX NPs were compared to each other by MTT assay of the treated MCF-7 cell lines. The results showed that the ζ-potential of F-Lys-MTX NPs was about −5.49 mV and the average size was 43.72 ± 4.73 nm. Model studies exhibited the release of MTX via peptide bond cleavage in the presence of proteinase K and at low pH. These studies specify that F-Lys-MTX NPs have a very remarkable anticancer effect, for breast cancer cell lines. [ABSTRACT FROM AUTHOR]

Abstract: In this work we reported the synthesis of tamoxifen (TMX) loaded l-tyrosine natural amino acids (Tyr) modified Fe3O4 magnetic nanoparticles. Tyr, which was containing phenol groups was selected to study their effects on biocompatibility, loading capacity and release profile of TMX. TMX loaded Tyr modified Fe3O4 magnetic nanoparticles (F@Tyr@TMX NPs) were characterized by X-ray diffraction, thermo gravimetric analysis, Fourier transform infrared spectroscopy, vibrating sample magnetometer, dynamic light scattering and transmission electron microscopy techniques. The results showed that the ζ-potential of F@Tyr@TMX NPs was about − 12.8 mV and the average size was 22.19 ± 3.58 [mean ± SD (n = 50)] nm. The loading capacity of 11.34 ± 0.09% and encapsulation efficiency of 51.21 ± 0.41%. Additionally, hemolysis test and MTT assays on HEK-293 were performed for determination of biocompatibility of F@Tyr@TMX NPs. Finally, the anticancer activity of F@Tyr@TMX NPs studied on MCF-7 breast cancer cell lines. The results indicate that these as prepared magnetic nanoparticles are suitable for delivery of TMX and even other hydrophobic drugs.Graphical Abstract: [ABSTRACT FROM AUTHOR]

In this study, a kind of magnetic Fe3O4@mTiO2-GO (where m was shorted mesoporous) hybrids with core–shell nano-structure for controlled dual targeted drug delivery was synthesized using a facile sono-chemical method. The structure and chemical composition of the nanocarrier (NC), and its surface morphology, were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM) with an energy dispersive X-ray (EDX), vibrating sample magnetometer (VSM) spectroscopy and Fourier transform infrared spectroscopy (FT-IR). Synthesis of Fe3O4@mTiO2-GO was proved by XRD and FT-IR. SEM showed that the particle size of this NC was in the range of ∼ 85–95 nm. EDX confirmed the presence of Ti, Fe, C and O in the nanocarrier. VSM analysis showed the magnetic behavior of the Fe3O4@mTiO2-GO nano-hybrids with saturation magnetization (MS) of 1.57 emu/g at room temperature. Curcumin (CUR) as a hydrophobic and an anti-tumor model drug was loaded on the NC. Drug loading capacity and encapsulation efficiency of this NC were as high as 17.85 and 72.45%, respectively. The drug release behavior was sustained and pH-responsive. MTT results demonstrated no significant cytotoxicity of the NC on Human Foreskin Fibroblast Normal cell line (HFF-2), indicating that this NC can be safe for use as a drug carrier for delivering anticancer drugs to tumor sites. The results of an MTT test on Caco-2 cancerous cells proved that CUR in nano-carriers has retained its anti-cancer properties. [ABSTRACT FROM AUTHOR]

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 vitrorelease 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 ofBCL-2, PARP, COX-2, Caspase-9andACTBgenes 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 thein vivopharmacokinetics of the SF-loaded micelles was carried out on SF-loaded PCL–PEG–PCL micelles in comparison with free SF. The results ofin vivoexperiments indicated that the SF loaded micelles significantly reduced the tumor size.In vivoresults 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. [ABSTRACT FROM PUBLISHER]

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]

Methotrexate is one of the most effective drugs that is commonly used in the treatment of cancer. However, its application is limited due to low solubility, high toxicity and rapid metabolism. Therefore, in the present study, worm-like polymeric nanoparticles as carrier of methotrexate were prepared using biodegradable copolymers (mPEG–PCL). The impact of nanoparticles’ geometry on the loading, delivery and drug’s anti-cancer activity was investigated. The di-block copolymer mPEG–PCL was being synthesized by a ring opening polymerization of ɛ-caprolactone in the presence of mPEG as the initiator and Sn(oct)2 as the catalyst. It was used for the preparation of worm-like micelles and coated with silica, so that their structures are stable after drying. The synthesized copolymers and nanoparticles were characterized by FTIR, HNMR, GPC, XRD, TGA, DLS, and FE-SEM analyses. The efficiencies of drug loading and release of nanoparticles as in vitro, was studied by high performance liquid chromatography. The MTT method was used to estimate the toxicity on MCF-7 cell category. The obtained results showed that the nanoparticles were worm-like particles with less than 150 nm diameter and about 1 µm length. The loading and encapsulation efficiencies of drug by the worm-like nanoparticles were 3.5 ± 0.14% and 65.6 ± 0.12%, respectively, while they were obtained as 2.1 ± 0.08% and 26 ± 0.10%, respectively, for spherical nanoparticles. The methotrexate diffusional behavior of worm-like nanoparticles was compared with that of the spherical ones. On the other hand, the anti-cancer activity of MTX-loaded nanoparticles was more than the free drug. The results of the MTT assay showed strong and dose-dependent inhibition of cell (MCF-7 category) growth by the nanoparticles compared with MTX. The inhibitory concentrations (IC50 i.e. reduction viability of cell to 50%) obtained for worm-like, spherical nanoparticles and free drug (incubation times 72 h) were 8.25 ± 0.20, 9.15 ± 0.17, 12.28 ± 0.15 µg/mL, respectively. It can be concluded that application of non-spherical nanoparticles is a better and more effective strategy for controlled and slow release of methotrexate in the treatment of cancer. [ABSTRACT FROM AUTHOR]

The Clavulanic acid (CLV) is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. In the present study, a reliable drug delivery system using poly (ε-caprolactone)-poly (ethylene glycol)-poly (ε-caprolactone) (PCL-PEG-PCL) was synthesized and the release profile of the CLV from the drug-loaded polymersomes was evaluated. In this study, CLV was encapsulated within PCL-PEG-PCL nanoparticles by a double emulsion technique (w/o/w), leading to creation of CLV-loaded PCL-PEG-PCL (CLV/PCL-PEG-PCL) polymersomes. Characterization, stability of polymersomes, the particle size was determined by DLS. The release profile of the CLV from the polymersomes which ready by the drug-loaded copolymer, was evaluated. Our studies resulted in a successful establishment of uniformity and spherical CLV-loaded PCL-PEG-PCL polymersomes. The loading efficiency of CLV was 16.00 ± 1.45%. The results of DLS show that the polymersomes have spherical shapes with size of 113 nm. In vitro release of CLV from CLV-entrapped polymersomes was remarkably sustained. The results indicate the successful formulation of curcumin loaded PCL-PEG-PCL polymersomes. [ABSTRACT FROM AUTHOR]

Purpose: Among the potent anticancer agents, curcumin is known as a very efficacious against many different types of cancer cells, but its clinical applications has been limited because of hydrophobicity, low gastrointestinal absorption, poor bioavailability and rapid metabolism. In this way, a novel micellar delivery system with mPEG-PCL was synthesized and the release profile of the curcumin from the drug-loaded micelles was evaluated. Methods: In this study, curcumin was encapsulated within monomethoxypoly(ethylene glycol)-poly(e-caprolactone) (mPEG-PCL) micelles through a single-step nano-precipitation method, leading to creation of curcumin-loaded mPEG-PCL (Cur/mPEG-PCL) micelles. Diblock mPEG-PCL copolymers were synthesized and used to prepare micelles. mPEG-PCL copolymer was characterized in vitro by HNMR, FTIR, DSC and GPC techniques. Then, mPEG-PCL copolymers with curcumin were self-assembled into micelles in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). Results: The findings showed the successful formation of smooth and spherical curcuminloaded micelles. The encapsulation efficiency of curcumin was 88 ± 3.32%. The results of AFM revealed that the micelles have spherical shapes with size of 73.8 nm. The release behavior of curcumin from micelles was compared in different media. In vitro release of curcumin from curcumin-entrapped micelles was followed remarkably sustained profile. The sustained release of drug was hypothetically due to the entrapment of curcumin in core of micelles. Conclusion: The results indicate the successful formulation of curcumin loaded m- PEG/PCL micelles. From the results, iIt can be concluded that curcumin m-PEG-PCL micelles may be considered as an effective treatment strategy for cancer in the future. [ABSTRACT FROM AUTHOR]

In this study we described the production of curcumin (CUR) loaded L‐tyrosine (Tyr coated Fe3O4 magnetic nanoparticles. CUR loaded Tyr modified Fe3O4 nanoparticles (F@Tyr@CUR NPs) were analyzed by transmission electron microscopy, fourier transform infrared spectroscopy, thermo gravimetric analysis, vibrating sample magnetometer, X‐ray diffraction and dynamic light scattering techniques. The dynamic light scattering results showed that the ζ‐potential of F@Tyr@CUR NPs was about −15.4 mV. Also, the internal average size was about 25.81 ± 3.31 (mean ± SD (n = 30)) nm. The drug loading and encapsulation efficiency were 8.87 ± 0.09% and 35.21 ± 0.41%, respectively. In addition, hemolysis test on human red blood cells were conducted to determine the hemocompatibility of F@Tyr@CUR NPs. Next, MTT assays on HEK‐293 were conducted to determine the toxicity of F@Tyr@CUR NPs. Lastly, the potential anticancer effect of F@Tyr@CUR NPs was considered on MCF‐7 cancer cell line. The outcomes indicated that these F@Tyr@CUR NPs are appropriate for delivery of CUR anticancer drug. Also, the MRI training established the effectiveness of Fe3O4 magnetic nanoparticles as contrast agent for the revealing of tumor as evidenced from the phantom images as well as higher T2 relaxivity. We have identified and developed a biocompatible drug delivery system (F@Tyr NPs), which could be used to delivery of chemotherapeutic agents such as CUR. Also, the MRI study demonstrated the effectiveness of Fe3O4 nanoparticles as contrast agent for the early detection of tumor as evidenced from the phantom images as well as higher T2 relaxivity. [ABSTRACT FROM AUTHOR]

In the present study, we successfully synthesized nanocarriers (NCs) based on Y-shaped miktoarm copolymers, Poly Ethylene Glycol-Lysine-(Poly Caprolactone) 2 (PEG-Lys-PCL 2), which were loaded by baicalein (B) through the nanoprecipitation process to assess their in-vitro and in-vivo properties. We applied various methods and measurements including proton nuclear magnetic resonance (HNMR), dynamic light scattering (DLS), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), MTT assay, hemolysis test, lethal dose, real-time PCR, and Morris water maze. The results of DLS indicated that the size and zeta potential of the obtained NCs and B-loaded NCs were acceptable. Also, in-vivo and in-vitro biocompatibility examinations proved that miktoarm-based NCs were safe, and all rats treated with miktoarm-based NCs did not exhibit any remarkable weight loss during the experiment. The results of the Morris water maze (in-vivo test) revealed that the normal saline-treated group, as well as B-miktoarm + Scopolamine (M + B + S) and B-miktoarm-Tween80 + Scopolamine (M + B + T + S) pretreatment groups, spent more time in the target quadrant. Thus, this experiment showed that pretreatment of rats with M + B + S and M + B + T + S had the most effects on spatial memory. According to quantitative PCR analysis, we hypothesized that, in comparison with other experimental groups, pretreatment of rats with M + B + T + S could be more effective in preventing cholinergic dysfunction, brain oxidative stress and cognitive deficits which cause by Scopolamine HBr. This outcome may be partially due to the upregulation of DHCR24, SELADIN, and SIRT6 in entire of the hippocampal region of normal saline-treated and M + B + T + S pretreatment groups. These results may be because mimicking the cell membrane structure would be an excellent feature for miktoarm, and partial coating of Tween-80 can play a critical role for PEG-Lys-PCL 2 -based NCs in crossing the brain cell membrane, and they can easily be uptaken by the cells. Eventually, all of the obtained data confirmed that PEG-Lys-PCL 2 miktoarm star copolymers are suitable for delivering therapeutic agents to the brain for the treatment of Alzheimer's disease (AD). Also, it seems that baicalein should be taken into account as a potent compound for the treatment of AD. [ABSTRACT FROM AUTHOR]

Abstract The present paper aimed to synthesize, using thermal-treatment method, a variety of Co 1-X Zn x Fe 2 O 4 -based nanocarriers (NCs) as Dual-controlled and targeted drug delivery systems (DDS) and provide a new structure as NCs suitable for the loading and pH-responsive characteristics of the chemotherapeutic curcumin (CUR). To study the structure, surface morphology, surface charge and magnetic properties of NCs, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), Zetasizer and vibrating sample magnetometer (VSM) were applied here. TEM images of Co 0.2 Zn 0.8 Fe 2 O 4 (Co-0.2) showed that NCs had a uniform spherical mesoporous morphology with an average grain size of about ∼17 nm. Also, it was found that Drug loading was very high, about 22.70 and 21.99 for Co 0.6 Zn 0.4 Fe 2 O 4 (Co-0.6) and Co 0.4 Zn 0.6 Fe 2 O 4 (Co-0.4), respectively. As indicated, NCs had highly pH-dependent drug release behavior, although different and unique in every one of them, which could be related to zeta potential of Co-0.6. In fact, the neutral zeta potential of Co-0.6 became positive when the pH of releasing media changed from 7.4 to 5.5. Consequently, the hydrogen bond between the Co-0.6 and CUR brake. Therefore, as expected, drug releasing varied from Co-0.6 to about 54% at pH 5.5, rather 29% at pH 7.4. To determine the cytotoxicity of NCs, hemolysis assay, MTT assay and acute toxicity test were used. The tests showed that NCs had the least in vitro and in vivo cytotoxicity and NCs, as a result, could be regarded to be nontoxic. MTT results demonstrated that drug loaded NCs had the same cell viability as bare drugs. Then, it can be concluded that these NCs have the potential required to act as drug delivery systems for anti-cancer drugs delivery such as CUR. Highlights • Co 1−X Zn x Fe 2 O 4 based nanocarriers (NCs) as Dual controlled targeted drug delivery systems (DDS) were synthesized. • Zeta potential at different pH, could control the release of CUR from NCs. • We controlled the release of CUR from NCs with replacing appropriate ratio of Zn and Co instead of Fe. • NCs had great in vivo and in vitro biocompatibility. • Small size of drug loaded-NCs and their stability can help to accumulate drugs in tumor site. [ABSTRACT FROM AUTHOR]

Abstract This study manipulated a chrysin loaded bovine serum albumin nanoparticles (BSA NPs), which could solubilize the poorly water-soluble drug and increase the therapeutic efficacy of the drug. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid which have some significant biological effects on the processes of chemical defense. Chrysin loaded bovine serum albumin nanoparticles (Chrysin-BSA NPs) were synthesized by a simple desolvation procedure. The resultant Chrysin-BSA NPs showed a spherical shape, with a diameter of 97.5 ± 5.75 nm (mean ± SD) nm and a ζ-potential of - 11 mV. The in vitro drug release study of chrysin presented 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. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. The in vitro cytotoxicity of the nanoparticles was performed by MTT assay on MCF-7 cancer cells. These results suggest that Chrysin-BSA NPs are a new drug delivery system for cancer therapy. Graphical abstract Unlabelled Image Highlights • The bovine serum albumin nanoparticles were prepared through desolvation process. • The resultant Chrysin-BSA NPs showed a spherical shape, with a diameter of 97.5 ± 5.75 nm. • Hemolysis assay and cytotoxicity study results show that BSA NPs are biocompatible. Therefore, the prepared Chrysin-BSA NPs is a promising drug delivery system for chrysin. [ABSTRACT FROM AUTHOR]

This work described a folic acid conjugated delivery of chrysin-loaded bovine serum albumin nanoparticles, which could overcome the nonspecific targeting disadvantage. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid which have some significant biological effects on the processes of chemical defense. Chrysin loaded bovine serum albumin nanoparticles (Chrysin-BSA NPs) were synthesized by a simple desolvation procedure. Afterward, folic acid (FA) was conjugated to the surface of Chrysin-BSA NPs by carbodiimide chemistry (Chrysin-BSA-FA NPs). The resultant Chrysin-BSA-FA NPs showed a spherical shape, with a hydrodynamic diameter of 97.5 ± 5.8 nm (mean ± SD) nm and a ζ-potential of −11.3 mV. The in vitro drug release study of chrysin presented a sustained and controlled release pattern. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. Both the Chrysin-BSA NPs and Chrysin-BSA-FA NPs prompted an enhanced cancer cell cytotoxic effect in contrast to chrysin solution. These data recommended that the folate-modified chrysin -loaded vehicle, which demonstrated better biocompatibility and potential superiority, could be a suitable cancer therapy in targeting tumors in the future. [ABSTRACT FROM AUTHOR]

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 ± 16.75 nm (mean ± SD) nm and a ζ-potential of – 9.19 mV. 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. [ABSTRACT FROM AUTHOR]

Amphiphilic FA-L-PEG-PCL (PEG: Poly ethylene glycol-hydrophilic segment, FA: Folic acid-targeting agent, L: Lysine-linker, PCL: Poly caprolactone-hydrophobic segment) copolymer was synthesized. Proton nuclear magnetic resonance (HNMR), Fourier-transform infrared spectroscopy (FT-IR), Dynamic light scattering (DLS), atomic force microscopy (AFM), dynamic scanning colorimetry (DSC) were used for characterization of synthesizes copolymers. For determining cytotoxicity of our copolymers, we used from MTT assay, Hemolysis assay and lethal dose 50 (LD50) test. These tests revealed that copolymers had least in vitro and in vivo cytotoxicity and they are categorized as practically none toxic. These copolymers were self-assembled into Round-shaped folate-functionalized micelles in aqueous medium for the folate receptor (FR)-mediated targeted delivery of Tamoxifen (TMX)-the anticancer drug- to cancer cells. The drug loading capacity and in vitro pH responsive controlled release performance showed that these micelles had potential as drug delivery systems (DDS) for hydrophobic anti-cancer drugs such as TMX. FA-L-PEG-PCL micelles was non-cytotoxic in high concentrations. Loaded-TMX micelles obviously showed an increase in killing of the cancer cells. [ABSTRACT FROM AUTHOR]

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 ± 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. [ABSTRACT FROM AUTHOR]