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.
In this study, nano-formulation has been used to tackle one of the most important environmental problems which can be considered a major threat to human health. We prepared some eco-friendly nanostructured lipid carriers (NLCs) as delivery agents to properly deliver an antibacterial agent (eugenol) into hospital wastewater in order to control bacterial growth. Eugenol-loaded nanostructured lipid carriers were prepared by hot high-speed homogenization. Then, the prepared nanocarriers were characterized using different techniques such as transmission electron microscopy, Fourier transform infrared, and dynamic scanning calorimetry. The turbidity assay and colony counting method were used to determine the ability of the prepared eugenol-loaded nanostructured lipid carriers to inhibit bacterial growth rate in the culture media and hospital wastewater, respectively. The mean size and zeta potential of NLC-eugenol were 78.12 +/- 6.1 nm and -29.43 +/- 2.21 mV, respectively. The results showed that the highest inhibitory effect of NLC-eugenol in culture media was seen in standard and wild Staphylococcus aureus strains (43.42% and 26.41%, respectively) with a concentration of 0.125 mu M. The antibacterial activity of NLC-eugenol in sterile wastewater on wild strains of bacteria showed that the most effective concentration to reduce bacterial amounts was 0.125 mu M on wild S. aureus and Enterococcus faecalis strains (38% and 33.47%, respectively) at 37 degrees C. The NLC-eugenol with a concentration of 0.125 mu M showed the greatest effect of reducing total microbial agents by 28.66% in hospital wastewater at 25 degrees C. The highest antibacterial effect achieved using the 0.125 mu M concentration is due to the egel phenomenon. Also, the mechanism of action of NLC-eugenol is cell wall destruction and eventually cell death. The results showed that NLC-eugenol with a concentration of 0.125 mu M can reduce wild bacterial strains in sterilized wastewater and hospital wastewater, which can prove the great potential of the prepared eugenol-loaded nanostructured lipid carriers to control bacterial growth. Practitioner Points NLC is one of the safest biodegradable and environmentally friendly carriers, which is nontoxic for humans and the environment. Eugenol is a natural compound, which makes it less toxic for the environment while being toxic for bacteria. Therefore, our method has the least side effect in comparison with existing methods for wastewater treatment. The gradual release of eugenol from NLC nanoparticles can effectively control the pathogenic factors of wastewater.
In this project, in vitro and in vivo properties of drug loaded nanocarriers based on miktoarm star copolymer mPEG-Lys-PCL2 were evaluated. Miktoarm was synthesized using ring opening polymerization reaction. Then, quercetin which is a hydrophobic plant based flavonol, was loaded into star NCs using nanoprecipitation method. The structure and biocompatibility nanocarriers were determined using proton nuclear magnetic resonance, Fourier-transform infrared spectroscopy, dynamic light scattering, hemolysis assay and lethal dose test. According to biocompatibility tests, prepared nanocarrier was practically nontoxic. The drug loading and encapsulation efficiency of nanocarriers were high because of miktoarm has two hydrophobic arms and more spaces between layers in comparison with linear copolymer with the same material. The results of MTT assay proved that quercetin-loaded star nanocarriers possess acceptable toxicity on cancerous cells which is because of the ability of miktoarm to mimic phospholipid structure. Furthermore, in vivo results showed the quercetin-loaded star nanocarriers is more effective to inhibit tumor volume than the free Quer. Also, the survival rate of mice treated with quercetin loaded star nanocarriers enhanced so that all the treated mice survived more than 75 days, and 20% of them were alive even after 85 days of experiment.
This review provides a summary of recent progress in the development of different nano-platforms for the efficient synergistic effect between photodynamic therapy and chemotherapy. In particular, this review focuses on various methods in which photosensitizers and chemotherapeutic agents are co-delivered to the targeted tumor site. In many cases, the photosensitizers act as drug carriers, but this review, also covers different types of appropriate nanocarriers that aid in the delivery of photosensitizers to the tumor site. These nanocarriers include transition metal, silica and graphene-based materials, liposomes, dendrimers, polymers, metal–organic frameworks, nano emulsions, and biologically derived nanocarriers. Many studies have demonstrated various benefits from using these nanocarriers including enhanced water solubility, stability, longer circulation times, and higher accumulation of therapeutic agents/photosensitizers at tumor sites. This review also describes novel approaches from different research groups that utilize various targeting strategies to increase treatment efficacy through simultaneous photodynamic therapy and chemotherapy.
In this paper, five different nano-platforms were synthesized by combining different ratios of cobalt, manganese, and iron to obtain an efficient photosensitizer for the treatment of breast cancer. Bovine serum albumin was used as a bio coating agent to improve the biocompatibility of the prepared nanoplatforms. Moreover, curcumin as an herbal anticancer agent was attached to albumin by a hydrazone pH-sensitive linker to improve the efficiency of drug delivery and obtain the synergistic effect of photodynamic therapy and chemotherapy. Different analysis methods including X-ray diffractometer, energy dispersive X-ray, ultraviolet-visible spectroscopy, field emission-scanning electron microscopy, Fourier-transform infrared spectroscopy, vibrating sample magnetometer, and thermogravimetric analysis were used to characterize the synthesized photosensitizers. After the identification and initial evaluation of their in vitro and in vivo properties, Co 0.5 was selected to be coated with bovine serum albumin to improve its biocompatibility, and the related tests confirm this fact. Further studies revealed that the cell viability of curcumin-loaded bovine serum loaded @ nano-platforms decreased to 40% in the presence of visible light at the concentration of 1000 lg/mL. These results can prove the great potential of bovine serum albumin and curcumin to improve the photodynamic performance of nano-platforms. (c) 2022 Elsevier B.V. All rights reserved.
In this project, different photosensitizers were prepared using different ratios of nickel, manganese, and iron. Then, multiple analysis were performed to evaluate their efficiency, and the most suitable one was used to be coated by hyaluronic acid to improve the nano-platform's biocompatibility and target ability. Moreover, another chemical targeting agent (riboflavin) was used to further improve the target ability of the prepared nano-platform. Different spectroscopies and thermal analysis were used to determine the physical and chemical characteristics of the prepared nano-platform. Also, in order to determine the biocompatibility of the nano-platform, in vitro and in vivo tests such as blood hemolysis, blood aggregation and lethal dose were performed. Then, an anti-cancer agent (curcumin) was loaded on the selected nano-platform to makes us able utilizing the synergistic effect of chemotherapy and photodynamic therapy simultaneously. Finally, the cell cytotoxicity results showed that the prepared nano-platform had a great anti-cancer potential which can make it a great candidate as a dual photo and chemo therapy agent for treatment of breast cancers.
In this research, the antibacterial effect of curcumin entrapped in polymeric nanoparticles (mPEG-PCL/curcumin) on resistant bacteria were investigated. Ring-opening polymerization method was used for the synthesis of mPEG-PCL copolymers at 120 °C. mPEG-PCL and Sn (Oct)2 were used as initiator/catalyst respectively. Curcumin loaded polymeric nanoparticles were prepared using the nanoprecipitation method. The particle size and zeta potential of mPEG-PCL/curcumin were found to be 111.16 ± 3.26 nm and − 5.67 ± 5.26 mv, respectively. TEM, AFM, FTIR and DSC were used to determine the structure of polymeric nanoparticles. The impact of mPEG-PCL/curcumin on wild (w) and standard (s) strains in bacterial media was assessed through the procedures of turbidity assay and colony-forming based on units per milliliter (CFU/mL). The impact of mPEG-PCL/curcumin on wild (w) strains in main wastewater was assessed by colony-forming based on units per milliliter (CFU/mL). mPEG-PCL/curcumin at a concentration of 40 µM had a stronger effect on wild strains of bacteria at 37 °C. However, examination of the performance of mPEG-PCL/curcumin in wastewater showed that mPEG-PCL/curcumin can reduce the total microbial total count at a concentration of 0.125 µM and at 25 °C.
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.
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.
The present study aimed to synthesize AgFeO2 nanocarriers by a thermal treatment method and to WA them with respect to their applicability in photodynamic therapy and drug delivery of anti-cancer drugs. Chemical structure, surface morphology, and magnetic properties of AgFeO2 were studied by X-ray diffractometer, Field emission-scanning electron microscopy, Fourier-transform infrared spectroscopy, and vibrating-sample magnetometer. The X-ray data for AgFeO2 indicated the typical patterns of rhombohedral phase with delafossite structure. The biocompatibility of AgFeO2 was evaluated by a hemolysis WA and a lethal dose test. The results confirmed the non-toxicity of the nanoparticles when used in photodynamic therapy. The loading and encapsulation efficiency of AgFeO2 were 20.23 +/- 0.24 and 84.55 +/- 1.24, respectively. Furthermore, when the pH of the release media decreased from 7.4 to 5.8, the release rate of the Quercetin from Quercetin loaded AgFeO2 increased from 52 to 70%. In the photodynamic therapy, the cytotoxicity of Quercetin, AgFeO2 and Quercetin-loaded AgFeO2 on tumor cells was studied. Cytotoxity of tumor cells treated with AgFeO2 and Quercetin loaded AgFeO2 under UV light significantly decreased from 65.7 to 27.2% to 23.58, and 7.6%, respectively. The results suggest that AgFeO2 is a suitable nanocarrier to be used in drug delivery and photodynamic therapy.
The graphene-based additives containing polyethyleneimine (PEI) or hydroxyapatite (HAP) were synthesized and their effects on the flame retardancy, thermal, mechanical properties of polyvinyl alcohol (PVA) matrix were evaluated. Thermogravimetric analysis studies (TGA) and Scanning electron microscope (SEM) images were indicated that PEI and HAP have a strong influence on the fire behavior of the composites which might be explained by the forming of a uniform and compact char during combustion. The presence of nitrogen in PEI and phosphorus in HAP which are generated nonflammable gases and phosphoric radicals, respectively at combustion conditions could represent a significant role in the catalytic char residue formation, heat transfer limitation and then diminish or even stop the combustion reactions. The char yields of the 5 wt% PVA/GO-PEI nanocomposites were increased up to 22 folds without any significant change in mechanical properties; Moreover, the char yield of PVA/GO-HAP nanocomposites was more than pure PVA (24 folds) because of its thermal stability at high temperature. All these data demonstrated that not only did PVA/GO-PEI keep the mechanical properties nearly the same as in pure PVA but also improved flame retardancy. But, the PVA/GO-HAP has great potential as flame retardants between all obtained composites.
In this project FA-L-PEG-PCL (FA: Folic acid, L: Lysine, PEG: Polyethylene glycol, PCL: Polycaprolactone) polymeric nanocarriers (NCs) were synthesized. In aqueous medium, this polymeric NCs could be self-assembled to form Round-shaped folate-functionalized micelles for delivery of Tamoxifen (TMX) and Quercetin (QUER) to cancerous cells. For determining the structure of this copolymer, fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and zeta sizer were used. The cytotoxicity of NCs was determined by hemolysis assay and this test displayed that the cytotoxicity of NCs is lower than 3%. To determine anticancer activity of synthesized drug loaded nanocarriers in vitro cell cytotoxicity analysis were performed on 4T1 cell line and in vivo treatment of tumors. Beside, histopathological study was performed to investigate the effect of drug loaded NCs on mice tissues. In vitro MTT experiment showed that QUER has significant synergistic effect for decreasing viability of the cancerous cell line (4T1); moreover, as an in vivo treatment of tumors, the FA-L-PEGPCL-TMX-QUER exhibited a clear tumor-inhibiting effect; therefore, according to this results, we can conclude that The FA-L-PEG-PCL-TMX-QUER NCs had a considerable potential for oral delivery of combination drugs having most clinical application.
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.
The problems associated with hydrophobic anticancer drugs are among the most important challenges to achieve efficient therapeutics for cancer treatment. In this study, PEGylated curcumin was used as the surface modification of magnetic nanoparticles (MNP@PEG-Cur) in order to simultaneously take advantage of magnetic targeting characteristic of nanoparticles and PEG conjugated drug. Curcumin was conjugated through EDC/NHS chemistry to the PEG hydroxyl functional groups, and then physically decorated on the surface of magnetic nanoparticles (MNP). The analysis of the conjugate and nanoparticles by FT-IR, 1HNMR, FE-SEM, TEM, EDX, TGA and VSM confirmed the successful synthesis and proper physicochemical properties of MNP@PEG-Cur nanoparticles. The carrier showed pH dependent drug release profile with higher drug release at acidic media (pH = 5.4) compared to neural condition (pH = 7.4). In addition, LD50 and hemolysis assay confirmed the biocompatibility of MNP@PEG-Cur. The cell viability assay also revealed that neither carrier, nor curcumin-loaded nanoparticles are cytotoxic at physiologic pH (7.4).
In the present study the effect of nanodiamond (ND) on the adsorption capacity of Drug has been investigated. Thermal oxidation nanodiamond (OND) was used as adsorbents for Methotrexate adsorption. The surface properties of NDs were studied by Fourier transform infrared spectroscopy and zeta potential. It was determined that thermal oxidation changed the surface properties of ND, including increase the amount of carboxylic acid groups and decreasing the zeta potential of ND by increasing the thermal oxidation time. The adsorption experiments showed that untreated ND (UND) has large adsorption capacity and fast adsorption kinetic for methotrexate (MTX). These results suggest that the adsorption behavior of UND with the MTX follows not only the charge but also the chemical interaction. Due to form the strong hydrogen bond between the carboxyl groups of MTX and the oxygen containing groups on the surface of NDs, Kinetic studies showed that the kinetic data are well fitted with the pseudo- second-order model for most of the adsorbents. MTT assay, Hemolysis assay and acute toxicity were used for determining biocompatibility of the adsorbents; MTT assay showed no significant toxicity up to near 300 µg/mL, OND showed neglectable hemolysis and acute toxicity result demonstrated OND was nontoxic.
In this project, a core-shell polymersome based on miktoarm star-copolymer:methoxy poly-ethylene glycol-lysine-(poly-caprolactone)2 was synthesized by a new method as controlled targeted drug delivery systems for codelivery of the chemotherapeutic methotrexate (MTX) and curcumin (CUR). Some properties of these nanocarriers (NCs), such as surface morphology, structure, surface charge, stability, and biocompatibility, were evaluated by proton nuclear magnetic resonance, dynamic scanning colorimetry, Fourier-transform infrared spectroscopy, dynamic light scattering, atomic force microscopy, critical aggregation concentration, hemolysis test, MTT assay, and lethal dose 50 (LD50). The AFM results showed that the uniform spherical morphology of NCs have an average size of about ∼60 nm. The drug loading of NCs was about 14.13 and 10.93% for CUR and MTX, respectively. The NCs revealed pH-sensitivity in drug release. The release of drugs from miktoarm-based NCs in neutral pH was lower than in acidic medium because of faster degradation of polymersome in acidic environment. MTT assay results showed that the drug-loaded NCs did not show significant toxicity due to which cell viability maintain over 82% at 300 μg/mL concentration. Also, synthesized miktoarm showed hemolysis lower than 3%. This result was repeated in LD50, and all mice which treat with 5000 mg/kg were still alive after 24 h. These result confirmed safety of miktoarm star copolymer. Eventually, the goal of this study is the application of water-soluble star copolymers miktoarm with pH dependent release properties for designing a new drug delivery carrier and using CUR for enhancing anticancer properties of MTX. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2817-2826, 2018.
Abstract 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. Graphical Abstract
Metal organic frameworks (MOFs) UiO‐66 (UiO stands for University of Oslo) and NH2‐UiO‐66 were prepared and characterized as sorbent (antidotal agents) for curcumin (CUR) adsorption. The structure of products were characterized by X‐ray powder diffraction (XRD), Field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), Attenuated Total Reflectance‐Fourier transform infrared spectroscopy (ATR‐FTIR), and N2 adsorption–desorption measurements. FESEM showed NH2‐UiO‐66 displayed symmetrical crystals with triangular base pyramid morphology, with the particle size around 100 nm and uniform size distribution. Adsorption capacities of CUR/MOFs with different mass ratios in the feed were investigated in the present study, and this investigation revealed that when the CUR/MOFs with mass ratio was around 0.4, the absorption capacity of NH2‐UiO‐66 had tended to maximum. Although, functionalization reduced the specific surface area and free volume, introducing polar amine groups could improve the affinity of NH2‐UiO‐66 respect to CUR. Kinetic studies showed that the kinetic data are well fitted with the pseudo‐ second‐order model. MTT assay revealed that MOFs at the concentration range of 0–560 μg/ml had no cytotoxic effect on the Human Foreskin Fibroblast normal cell line (HFF‐2). These results suggest that these MOFs could be safe as sorbent for adsorb CUR from the body.
Purpose: In this study, methoxy poly (ethylene glycol)-poly (epsilon-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 4h 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 -14.90.47mV and the average size was in range of 66.10 +/- 0.34nm. 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.
A low cytotoxic metal–organic framework (MOF) UiO-66 (UiO stands for University of Oslo) and NH2-UiO-66, that showed high cell viability of HFF-2 via 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium assay, was reported as an effective adsorbent (antidotal) agents. The structure of MOFs was confirmed by Fourier transform infrared, Field emission scanning electron microscopy (FESEM) and X-ray diffraction. Thermal behavior of MOFs was investigated using with thermogravimetric analyzer in nitrogen atmosphere to check the thermal stability. FESEM showed NH2-UiO-66 displayed symmetrical crystals with triangular base pyramid morphology, with the particle size around 100 nm and uniform size distribution. The specific surface areas were calculated using the Brunauer–Emmett–Teller method and surface area and total pore volume of NH2-UiO-66 were calculated to be 1258 m2/g and 0.51 cm3/g, respectively. Methotrexate salt (MTX) was selected as the model drug which was adsorbed into inner pores and channels of MOFs by diffusion manner. The interaction between MOFs and MTX and the effect of pH on interaction between them in aqueous solution was investigated. The final results showed that UiO-66 have high adsorbing capacity and great affinity to MTX.