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In The present project, a variety of MnFe 2 O 4 (Mn) and Cr 2 Fe 6 O 12 (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.

In this project methotrexate (MTX) conjugated albumin based nanoparticles (MTX-BSA) loaded with curcumin (CUR) drug (CUR-MTX-BSA) for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy were designed. Co-delivery is a new strategy which minimize the amount of each drug, reduce of side effects and also to achieve the synergistic effect for cancer therapies. The MTX was conjugated to albumin via covalent bond. Next, this synthesized prodrug loaded with CUR. Afterward, the formulations were evaluated for physical and chemical properties by DLS, TEM, FTIR, UV/Vis, DSC analysis, in vitro cytotoxicity and in vivo biocompatibility studies. Furthermore, the drug loading and release study were evaluated. Proteinase K enzyme was used to break amid bond between MTX and BSA and also amidic bonds in BSA structure. Administration of up to 2000 mg/kg of BSA to healthy animals was non-toxic and all treated mice were still alive after 24 h. The result of this study proved that CUR-MTX-BSA can be used as a proficient vehicle for effective co-delivery of CUR and MTX in the treatment of cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Natural products have been used for the treatment of various diseases such as cancer. Curcumin (CUR) and sulforaphane (SF) have anti-cancer effects, but their application is restricted because of their low water solubility and poor oral bioavailability. To improve the bioavailability and solubility of SF and CUR, we performed an advanced delivery of SF and CUR 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 nanocarrieris evaluated by, transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). The results revealed that the size of NPs was 20 nm. They were mono-dispersed in water, with high drug-loading capacity and stability. CUR and SF were encapsulated into NPs with loading capacity of 16.32±0.023% and 15.74±0.015% and entrapment efficiency of 74.57±0.14% and 72.20±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 (SK-BR-3) 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 void CUR. The results of flow cytometry and real-time PCR shown that nano-carriers can increase therapeutic effects of SF and CUR by apoptosis and necrosis induction as well as inhibiting of migration in SK-BR-3 cell line., Competing Interests: Conflict of Interest: The authors report no declarations of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. A conjugate of the antitumor drug, doxorubicin, with diblock methoxy poly (ethylene glycol)-poly caprolactone (mPEG-PCL) copolymer was synthesized by the reaction of mPEG-PCL copolymer with doxorubicin in the presence of p-nitrophenylchloroformate. The conjugated copolymer was characterized in vitro by 1 H-NMR, FTIR, DSC and GPC techniques. Then, the doxorubicin conjugated mPEG-PCL(DOX-mPEG-PCL) was self-assembled into micelles in the presence of curcumin in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM).The encapsulation efficiency of doxorubicin and curcumin were 82.31 ± 3.32 and 78.15 ± 3.14%, respectively. The results revealed that the micelles formed by the DOX-mPEG-PCL with and without curcumin have spherical structure with average size of 116 and 134 nm respectively. The release behavior of curcumin and doxorubicin loaded to micelles were investigated in a different media. The release rate of micelles consisted of the conjugated copolymer was pH dependent as it was higher at lower pH than in neutral condition. Another feature of the conjugated micelles was a sustained release profile. The cytotoxicity of micelles were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, atetrazole) assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the mPEG-PCL copolymer did not affect the growth of A549 cells. The cytotoxic activity of the micelles against A549 cells was greater than free doxorubicin and free curcumin.

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, a biocompatible block copolymer including poly ethylene glycol and poly caprolactone was synthesized using ring-opening reaction. Then, the copolymer was conjugated to folic acid using lysine as a linker. Also, curcumin (CUR) was used as a therapeutic anticancer agent. Nanoprecipitation method was used to prepare CUR-loaded polymeric micelles. Different methods including Fourier-transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the prepared nanocarriers (NCs). MTT assay and hemolysis assay were used to evaluate in vitro anticancer efficiency and biocompatibility of the prepared NCs, respectively. The results proved efficiency of NCs as a drug delivery system (DDS) in various aspects such as physicochemical properties and biocompatibility. Also, in vivo results showed that NCs did not show any severe weight loss and side effects on mice, and the anti-cancer study results of the CUR-loaded NCs proved that the conjugation of folic acid on the surface of NCs as a targeting agent could increase the therapeutic efficacy of 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]

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. [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]

Triblock poly(ε-caprolactone) - poly(ethylene glycol) - poly(ε-caprolactone) (PCL-PEG-PCL) copolymers were synthesized and used to prepare polymersomes for controlled release of lovastatin (LOV) as hydrophobic drug. Biodegradable PCL-PEG-PCL copolymer nanoparticles were prepared and the drug loading, release, release kinetics, and anti-cancer activity of these drugs was investigated. The PCL-PEG-PCL copolymer was synthesized by ring-opening polymerization of e-caprolactone in the presence of mPEG as the initiator and Sn(Oct)2 as the catalyst. The synthesized copolymers and nanoparticles were characterized by FTIR, 1H NMR, DLS, and AFM techniques. The efficiency of drug loading and release from nanoparticles in vitro was studied by UV-Vis spectrophotometry. Additionally, MTT assays on HFF-2 cell lines were performed for determining the biocompatibility of polymersomes. Finally, the antiproliferative activity of polymersomes was examined on MCF-7 breast cancer cell line. The obtained results showed that the average diameter of nanoparticles was less than 57 nm. The loading capacity and encapsulation efficiency of LOV was 16.1 ± 0.36% and 59.01 ± 0.78%, respectively. In vitro release study showed that the release rate of polymersomes depended on pH and was higher at lower pH than under neutral condition. The result of cell viability assay on the MCF-7 line proved that bare nanoparticles showed little inherent cytotoxicity whereas the LOV-loaded nanoparticles were cytotoxic. [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]

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 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]

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]

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]