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1.
Pharm Dev Technol ; 26(8): 807-823, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34190000

RESUMEN

Malaria, as one of the most common human infectious diseases, remains the greatest global health concern, since approximately 3.5 billion people around the world, especially those in subtropical areas, are at the risk of being infected by malaria. Due to the emergence and spread of drug resistance to the current antimalarials, malaria-related mortality and incidence rates have recently increased. To overcome the aforementioned obstacles, nano-vehicles based on biodegradable, natural, and non-toxic polymers have been developed. Accordingly, these systems are considered as a potential drug vehicle, which due to their unique properties such as the excellent safety profile, good biocompatibility, tunable structure, diversity, and the presence of functional groups within the polymer structure, could facilitate covalent attachment of targeting moieties and antimalarials to the polymeric nano-vehicles. In this review, we highlighted some recent developments of liposomes as unique nanoscale drug delivery vehicles and several polymeric nanovehicles, including hydrogels, dendrimers, self-assembled micelles, and polymer-drug conjugates for the effective delivery of antimalarials.


Asunto(s)
Antimaláricos/uso terapéutico , Portadores de Fármacos , Malaria/tratamiento farmacológico , Nanotecnología/métodos , Antimaláricos/administración & dosificación , Resistencia a Medicamentos , Humanos
2.
Pharm Dev Technol ; 23(10): 1156-1167, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30320535

RESUMEN

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.


Asunto(s)
Aminoácidos/química , Medios de Contraste/química , Sistemas de Liberación de Medicamentos/métodos , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Supervivencia Celular , Portadores de Fármacos/química , Flavonoides/administración & dosificación , Células HEK293 , Hemólisis , Humanos , Neoplasias/diagnóstico por imagen
3.
Sci Rep ; 14(1): 13299, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858410

RESUMEN

Radiation therapy and phototherapy are commonly used cancer treatments that offer advantages such as a low risk of adverse effects and the ability to target cancer cells while sparing healthy tissue. A promising strategy for cancer treatment involves using nanoparticles (NPs) in combination with radiation and photothermal therapy to target cancer cells and improve treatment efficacy. The synthesis of gold NPs (AuNPs) for use in biomedical applications has traditionally involved toxic reducing agents. Here we harnessed dopamine (DA)-conjugated alginate (Alg) for the facile and green synthesis of Au NPs (Au@Alg-DA NPs). Alg-DA conjugate reduced Au ions, simultaneously stabilized the resulting AuNPs, and prevented aggregation, resulting in particles with a narrow size distribution and improved stability. Injectable Au@Alg-DA NPs significantly promoted ROS generation in 4T1 breast cancer cells when exposed to X-rays. In addition, their administration raised the temperature under a light excitation of 808 nm, thus helping to destroy cancer cells more effectively. Importantly, no substantial cytotoxicity was detected in our Au@Alg-DA NPs. Taken together, our work provides a promising route to obtain an injectable combined radio enhancer and photothermally active nanosystem for further potential clinic translation.


Asunto(s)
Alginatos , Neoplasias de la Mama , Oro , Nanopartículas del Metal , Oro/química , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Alginatos/química , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Línea Celular Tumoral , Animales , Ratones , Terapia Fototérmica/métodos , Fototerapia/métodos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Dopamina/química , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación
4.
Adv Biomed Res ; 12: 126, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37434917

RESUMEN

Background: Nanotechnology has introduced valuable carriers for vaccine delivery. The success of vaccination depends on many factors, such as the intact and safe presentation of vaccine candidates to immune cells. We have conjugated branched PEI-2k and oleic acid (OL) as the building block of the cationic micelle. We aimed to introduce a novel carrier for vaccine candidates. Materials and Methods: We conjugated polyethyleneimine and OL (POA) to synthesize the building blocks of cationic micelles. The critical micelle concentration (CMC), size and zeta potential of micelles, and their stability in 60 days were determined. Loading, encapsulation efficiency, and in vitro release study were assessed using bovine serum albumin (BSA) as a protein model. Furthermore, the cytotoxicity and hemocompatibility of developed nanosized micelles were evaluated to ascertain the biocompatibility of fabricated micelles. Cell uptake of cationic micelles in the macrophage cell line was also followed up. Results: The conjugation of two polymer parts was confirmed by Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance techniques. The CMC of the developed micelles was around 5.62 × 10-8 mg/ ml, whereas the loading and encapsulation efficiencies were 16.5% and 70%, respectively. The size and zeta potential of the cationic micelles were 96.53 ± 18.53 nm and 68.3 mV, respectively. The release of BSA from POA micelles after 8 and 72 hours was 8.5% and 82%, respectively. Finally, fluorescence microscopy showed that the prepared micelles were successfully and effectively taken up by RAW264.7 cells. Conclusion: These results may provide a cutting-edge vaccine delivery solution and open up a new avenue for future vaccine research.

5.
ACS Appl Bio Mater ; 6(3): 1019-1031, 2023 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-36862384

RESUMEN

Although chemotherapy is regarded as an essential option in cancer treatment, it is still far from being perfect. Inadequate tumor drug concentration and systemic toxicity along with broad biodistribution have diminished the utility of chemotherapy. Tumor-targeting peptide-conjugated multifunctional nanoplatforms have emerged as an effective strategy for site-directed tumor tissues in cancer treatment and imaging. Herein, Pep42-targeted iron oxide magnetic nanoparticles (IONPs) functionalized with ß-cyclodextrin (ßCD) containing doxorubicin (DOX) (Fe3O4-ßCD-Pep42-DOX) were successfully developed. The physical effects of the prepared NPs were characterized by employing various techniques. Transmission electron microscopy (TEM) images disclosed that the developed Fe3O4-ßCD-Pep42-DOX nanoplatforms had a spherical morphology and a core-shell structure with a size of nearly 17 nm. Fourier transform infrared (FT-IR) spectroscopy showed that ß-cyclodextrin, DOX, and Pep42 molecules were successfully loaded on the IONPs. In vitro cytotoxicity analysis revealed that the fabricated multifunctional Fe3O4-ßCD-Pep42 nanoplatforms possessed excellent biosafety toward BT-474, MDA-MB468 (cancerous cells), and MCF10A normal cells, while Fe3O4-ßCD-Pep42-DOX exhibited great cancer cell killing ability. The high cellular uptake along with intracellular trafficking of Fe3O4-ßCD-Pep42-DOX highlights the usefulness of the Pep42-targeting peptide. In vivo results strongly supported the in vitro results, i.e., significant tumor size reduction was observed by single-dose injection of Fe3O4-ßCD-Pep42-DOX into tumor-bearing mice. Interestingly, in vivo MR imaging (MRI) of Fe3O4-ßCD-Pep42-DOX revealed T2 contrast improvement in the tumor cells and therapeutic ability in cancer theranostics. Taken together, these findings provided strong evidence for the potential capability of Fe3O4-ßCD-Pep42-DOX as a multifunctional nanoplatform in cancer therapy and imaging and opens up a new avenue of research in this area.


Asunto(s)
Péptidos de Penetración Celular , Nanopartículas de Magnetita , Neoplasias , Animales , Ratones , Chaperón BiP del Retículo Endoplásmico , Nanopartículas de Magnetita/uso terapéutico , Nanopartículas de Magnetita/química , Ligandos , Espectroscopía Infrarroja por Transformada de Fourier , Distribución Tisular , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Neoplasias/tratamiento farmacológico
6.
Int J Biol Macromol ; 234: 123636, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36775221

RESUMEN

A wide range of high-Z nanomaterials are fabricated to decrease radiation dose by sensitizing cells to irradiation through various mechanisms such as ROS generation enhancement. Alginate-coated silver sulfide nanoparticles (Ag2S@Alg) were synthesized and characterized by SEM, TEM, DLS, XRD, EPS, FT-IR, and UV-vis analysis techniques. Cytotoxicity of nanoparticles was tested against HFF-2, MCF-7, and 4 T1 cell lines for biocompatibility and radio enhancement ability evaluation, respectively. Moreover, the hemolysis assay demonstrated that the nanoparticles were biocompatible and nontoxic. In vitro intracellular ROS generation and calcein AM/PI co-staining unveiled cancerous cell death induction by nanoradiosensitizer, Ag2S@Alg. Further, histopathology results emphasized the tumor ablation capability of Ag2S@Alg. Silver anticancer properties were also recognized and combined with its radiosensitizing effect under X-ray irradiation.


Asunto(s)
Neoplasias de la Mama , Nanopartículas del Metal , Humanos , Femenino , Alginatos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/patología , Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Especies Reactivas de Oxígeno , Nanopartículas del Metal/uso terapéutico
7.
Rev Bras Farmacogn ; 33(2): 310-315, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36687781

RESUMEN

Glycyrrhiza glabra L., Fabaceae, or licorice has shown potential therapeutic effects on fever, gastric ulcers, hepatic disorders, and malaria. This study aimed to assess the antimalarial activity of different fractions of root extract from twelve ecotypes from Iran. In this regard, mice were then randomly divided into 8 groups of 5 mice. Four hours after mice were infected by Plasmodium berghei, they received methanolic plant extract by intraperitoneal injection. The treatment was continued for 4 consecutive days (every 24 h), then on the fifth and seventh days, blood samples were taken from the tails of the mice and the parasitic percentages were calculated by microscopy technique. In comparison to control, every analyzed ecotype has a remarkable parasite inhibitory effect, whereas the source of the root also has a drastic difference in its antimalarial effects. The highest percentage of inhibition on days 5 and 7 was subjected to the extract of Semirom ecotype with suppression of 86.37 and 83%, respectively. On the other hand, 13.21 and 9.19% parasite growth inhibition was shown in the extracts of Shahrbabak and Haji Abad, respectively. The significant difference between these 12 ecotypes was shown with Mann-Whitney U pairwise comparison to variable parasitemia day 5 and parasitemia day 7 (p < 0.001). Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-022-00353-8.

8.
Int J Biol Macromol ; 233: 123273, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36646349

RESUMEN

Noble metals as high atomic number elements can localize X-ray radiation within tumor cells by exploiting different mechanisms. Here, alginate (Alg)-coated platinum nanoparticles (Pt@Alg) were synthesized, characterized, and implemented as a radiosensitizer to enhance X-ray therapeutic efficacy in breast cancer in vitro and in vivo. Alg not only improves the biocompatibility of the radioenhancer, but also stabilizes the nanoparticles. Pt@Alg was studied by different characterization methods including DLS, STEM, Fe-SEM, XRD, XPS, FT-IR and UV-Vis spectrophotometry. The nanosystem provided a higher level of intracellular ROS in malignant cells and enhanced cancer cell death under X-Ray irradiation. Clonogenic assay also demonstrated the radiosensitizing properties of the nanosystem, in vitro. In vivo result show tumor growth restraining properties of the nanosystem when it was administrated along with X-Ray irradiation. Histopathology results confirmed the impact of nanosystem and X-ray co-treatment, as well. Altogether, the importance of radiosensitizers for improving radiotherapy outcomes was highlighted.


Asunto(s)
Neoplasias de la Mama , Neoplasias Mamarias Animales , Nanopartículas del Metal , Nanopartículas , Fármacos Sensibilizantes a Radiaciones , Animales , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Alginatos/farmacología , Nanopartículas del Metal/uso terapéutico , Espectroscopía Infrarroja por Transformada de Fourier , Platino (Metal) , Fármacos Sensibilizantes a Radiaciones/farmacología , Neoplasias Mamarias Animales/tratamiento farmacológico
9.
Oxid Med Cell Longev ; 2023: 7643280, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36865347

RESUMEN

Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively. In vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously made the possibility of antioxidant effects on the brain in specific doses, which resulted in elevated spatial memory and learning along with cognitive function in Wistar rats. In addition, significantly lower MDA and PCO and higher levels of neural GSH and antioxidant levels were observed, while histopathological improvement was approved. The developed nanogel can be a suited vehicle for drug delivery of EDV to the brain and improve ischemia-induced oxidative stress cell damage.


Asunto(s)
Accidente Cerebrovascular Isquémico , Neuroprotección , Ratas , Animales , Ratas Wistar , Edaravona/farmacología , Edaravona/uso terapéutico , Nanogeles , Encéfalo , Glutatión , Isquemia , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Enfermedad Aguda
10.
J Biomater Sci Polym Ed ; 34(13): 1824-1842, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36869798

RESUMEN

Application of conventional chemotherapy regardless of its unique effectiveness have been gradually being edged aside due to limited targeting capability, lack of selectivity and chemotherapy-associated side effects. To this end, colon-targeted nanoparticles via combination therapy have shown great therapeutic potential against cancer. Herein, pH/enzyme-responsive biocompatible polymeric nanohydrogels based on poly(methacrylic acid) (PMAA) containing methotrexate (MTX) and chloroquine (CQ) were fabricated. PMAA-MTX-CQ exhibited high drug loading capacity of which MTX was 4.99% and was CQ 25.01% and displayed pH/enzyme-triggered drug release behavior. Higher CQ release rate (76%) under simulated acidic microenvironment of tumor tissue whereas 39% of CQ was released under normal physiological conditions. Intestinally, MTX release was facilitated in the presence of proteinase K enzyme. TEM image demonstrated spherical morphology with particle size of less than 50 nm. In vitro and in vivo toxicity assessments indicated that developed nanoplatforms possessed great biocompatibility. These nanohydrogels did not cause any adverse effects against Artemia Salina and HFF2 cells (around 100% cell viability) which highlight the safety of prepared nanohydrogels. There was no death in mice received different concentrations of nanohydrogel through oral administration and less than 5% hemolysis was found in red blood cells incubated with PMAA nanohydrogels. In vitro anti-cancer results showed that combination therapy based on PMAA-MTX-CQ can effectively suppress the growth of SW480 colon cancer cells (29% cell viability) compared to monotherapy. Altogether, these findings suggest that pH/enzyme-responsive PMAA-MTX-CQ could effectively inhibit cancer cell growth and progression via site-specific delivery of its cargo in a safe and controlled manner.


Asunto(s)
Neoplasias Colorrectales , Nanopartículas , Ratones , Animales , Metotrexato/farmacología , Cloroquina/farmacología , Polímeros , Sistemas de Liberación de Medicamentos/métodos , Concentración de Iones de Hidrógeno , Neoplasias Colorrectales/tratamiento farmacológico , Microambiente Tumoral
11.
J Control Release ; 353: 850-863, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36493951

RESUMEN

Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe2O4@BSA-FA-CUR, loaded with curcumin (CUR) and modified by bovine serum albumin (BSA) and folic acid (FA) was developed to enhance tumor accumulation and promote the anti-cancer activity while attenuating adverse effects. Both copper (Cu) and iron (Fe) were utilized in the construction of these submicron scale entities, therefore strong radiosensitization effect is anticipated by implementation of these two metals. The structure-function relationships between constituents of nanomaterials and their function led to the development of nanoscale materials with great radiosensitizing capacity and biosafety. BSA was used to anchor Fe and Cu ions but also to improve colloidal stability, blood circulation time, biocompatibility, and further functionalization. Moreover, to specifically target tumor sites and enhance cellular uptake, FA was conjugated onto the surface of hybrid bimetallic nanoparticles. Finally, CUR as a natural chemotherapeutic agent was encapsulated into the developed bimetallic nanoparticles. With incorporation of all abovementioned stages into one multifunctional nanoplatform, CuFe2O4@BSA-FA-CUR is produced for synergistic chemoradiotherapy with positive outcomes. In vitro investigation revealed that these nanoplatforms bear excellent biosafety, great tumor cell killing ability and radiosensitizing capacity. In addition, high cancer-suppression efficiency was observed through in vivo studies. It is worth mentioning that co-use of CuFe2O4@BSA-FA-CUR nanoplatforms and X-ray radiation led to complete tumor ablation in almost all of the treated mice. No mortality or radiation-induced normal tissue toxicity were observed following administration of CuFe2O4@BSA-FA-CUR nanoparticles which highlights the biosafety of these submicron scale entities. These results offer powerful evidence for the potential capability of CuFe2O4@BSA-FA-CUR in radiosensitization of malignant tumors and opens up a new avenue of research in this area.


Asunto(s)
Antineoplásicos , Curcumina , Nanopartículas , Neoplasias , Ratones , Animales , Antineoplásicos/uso terapéutico , Portadores de Fármacos , Neoplasias/tratamiento farmacológico , Quimioradioterapia
12.
Iran J Parasitol ; 17(2): 202-213, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36032752

RESUMEN

Background: The application of plumbagin (PLN), with a wide use in pharmaceutical science, is limited due to its low water solubility and poor bioavailability. Micelles can encapsulate hydrophobic drugs due to their hydrophobic core. The aim of this study was to develop and characterize a polymeric micelle formulation of PLN and evaluate its in vivo anti-plasmodial property. Methods: The study was conducted at Zanjan University of Medical Sciences, Zanjan, Iran in 2018. The triblock copolymeric micelles of PLN was prepared by e-caprolactone ring-opening polymerization, by PEG as the macroinitiator and using Sn(Oct)2 for its catalytic properties. The synthesized nanoparticles were characterized by 1H NMR, FTIR, GPC, AFM, and DLS. The encapsulation efficiency, drug loading capacity, and drug release were measured by UV-Vis at 520 nm. Also in vivo anti-plasmodial potential of fabricated drug loaded micelle was investigated using the 4-day suppressive test against Plasmodium berghei infection in mice. Results: The nanoparticles average diameter was obtained less than 80 nm. The loading capacity and encapsulation efficiencies were 18.9±1.3% and 81±0.78%, respectively. In vitro, PLN release studies showed a sustained-release pattern until 7 days in PLN-loaded micelles (M-PLN) and drug release rate in acidic condition was higher than neutral condition. In vivo, anti-plasmodial results against P. berghei displayed an 8-fold increase in anti-plasmodial activity of M-PLN when compared to free PLN at the tested dosage level on the 7th day. Conclusion: Based on these results, PCL-PEG-PCL micelles have a great potential to be the carrier for PLN for the malaria targeting.

13.
Int J Low Extrem Wounds ; 21(1): 18-30, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32524874

RESUMEN

Because of the intrinsic complexity, the classification of wounds is important for the diagnosis, management, and choosing the correct treatment based on wound type. Generally, burn injuries are classified as a class of wounds in which injury is caused by heat, cold, electricity, chemicals, friction, or radiation. On the other hand, wound healing is a complex process, and understanding the biological trend of this process and differences in the healing process of different wounds could reduce the possible risk in many cases and greatly reduce the future damage to the injured tissue and other organs. The aim of this review is to provide a general perspective for the burn wound location among the other types of injuries and summarizing as well as highlighting the differences of these types of wounds with emphasizing on factors affecting thereof.


Asunto(s)
Quemaduras , Quemaduras/terapia , Humanos , Cicatrización de Heridas
14.
Nanomedicine (Lond) ; 17(4): 201-217, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35037483

RESUMEN

Aim: The aim of the present investigation was to develop niosomes containing both curcumin (CUR) and methotrexate (MTX). Also, the combinational effect of CUR and MTX in both free and niosomal forms on growth inhibition potential and induction of apoptosis in the HCT-116 cell line were exploited. Materials & methods: Niosomes were prepared by the thin-film hydration method and their physicochemical properties were determined by various techniques. Cellular uptake, cell apoptosis, wound healing and MTT assay were conducted to ascertain niosomes' feasibility for cancer therapy. Results: The combination of CUR and MTX in niosomal formulation showed more toxicity than their combination in free form. Conclusion: The nanocarrier-based approach was effective for the codelivery of CUR and MTX against cancer cells in vitro.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Curcumina , Antineoplásicos/química , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Curcumina/química , Células HCT116 , Humanos , Liposomas/química , Metotrexato/química , Tamaño de la Partícula
15.
Iran J Basic Med Sci ; 25(12): 1477-1486, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36544521

RESUMEN

Objectives: In this study, Boltorn® H40-PEG-MTX-anti-VEGFR2 nanobody was fabricated in which nanobody was selected for blocking the receptor, H40 as a nanocarrier for delivery of methotrexate (MTX) to the tumor cells, and polyethylene glycol (PEG) moieties for improving the blood circulation time and safety. Materials and Methods: The synthesis process of the nanosystem has been characterized by different analytical methods. Results: The prepared nanoplatform exhibited high drug loading capacity, excellent colloidal stability, and an average particle size of around 105 nm. MTX was successfully conjugated through ester bonds and its release profile clearly showed that the ester bond is in favor of releasing the drug in acidic pH (5.5). The cytotoxicity of the developed nanoplatform exhibited great anti-cancer activity against MCF7 and KDR293 (cells with overexpressed anti-VEGFR2 NB receptors) cell lines while no deleterious toxicity was observed for nanocarrier against HEK293 normal cells. Furthermore, both hemolysis and LD50 assay results confirmed the hemocompatibility and biocompatibility of the developed nanoplatform. Conclusion: The most striking result to derive from the data is that the designed nanoplatform could potentially inhibit cell migration and invasion and the anti-angiogenesis properties of the developed nanoplatform may serve as a promising nanosystem to suppress the formation of blood vessels around tumor cells and consequently inhibit tumor progression.

16.
J Biomater Sci Polym Ed ; 33(3): 279-298, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34547988

RESUMEN

Multifunctional nanocarriers as a promising platform could provide numerous opportunities in the field of drug delivery. Drug carriers loaded with both magnetic nanoparticles (MNPs) and therapeutic agents would allow the combination of chemotherapy with the possibility of monitoring or controlling the distribution of the nano vehicles in the body which may improve the effectiveness of the therapy. Furthermore, by applying these strategies, triggering drug release and/or synergistic hyperthermia treatment are also reachable. This study aimed to explore the potential of the quercetin (QUR) loaded magnetic nano-micelles for improving drug bioavailability while reducing the drug adverse effects. The bio-safety of developed QUR loaded magnetic nano-micelles (QMNMs) were conducted via mitochondrial toxicity using isolated rat liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric reducing ability of plasma (FRAP). QMNMs with a mean particle size of 85 nm (PDI value of 0.269) and great physical stability were produced. Also, TEM images indicated that the prepared QMNMs were semi-spherical in shape. These findings also showed that the constructed QMNMs, as a pH-sensitive drug delivery system, exhibited a stable and high rate of QUR release under mildly acidic conditions pH (5.3) compared to neutral pH (7.4). The most striking result to emerge from the data is that an investigation of various mitochondrial functional parameters revealed that both QMNMs and QUR have no specific mitochondrial toxicity. Altogether, these results offer overwhelming evidence for the bio-safety of QMNMs and might be used as an effective drug delivery system for targeting and stimuli-responsive QUR delivery.


Asunto(s)
Micelas , Quercetina , Animales , Doxorrubicina , Portadores de Fármacos/toxicidad , Sistemas de Liberación de Medicamentos , Concentración de Iones de Hidrógeno , Fenómenos Magnéticos , Mitocondrias Hepáticas , Tamaño de la Partícula , Polímeros , Quercetina/toxicidad , Ratas
17.
J Biomater Appl ; 36(6): 1055-1063, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34304637

RESUMEN

In this research, magnetic nanostructured lipid carriers (Mag-NLCs) were synthesized for curcumin (CUR) delivery. NLCs are drug-delivery systems prepared by mixing solid and liquid (oil) lipids. For preparation of NLCs, cetylpalmitate was selected as solid lipid and fish oil as liquid lipid. CUR-Mag-NLCs were prepared using high-pressure homogenization technique and were characterized by methods including X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and dynamic light scattering (DLS). The CUR-Mag-NLCs were developed as a particle with a size of 140 ± 3.6 nm, a polydispersity index of 0.196, and a zeta potential of -22.6 mV. VSM analysis showed that the CUR-Mag-NLCs have excellent magnetic properties. Release rate of the drug was higher at 42 °C than 37 °C, indicating that release of the synthesized nanoparticles is temperature-dependent. Evaluation of mitochondrial toxicity was done using the isolated rats liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric- reducing ability of plasma (FRAP) assays to study biosafety of the CUR-Mag-NLCs. Results of In vitro study on the isolated mitochondria revealed that both CUR-Mag-NLCs and curcumin have no specific mitochondrial toxicity.


Asunto(s)
Curcumina , Nanopartículas , Nanoestructuras , Animales , Curcumina/toxicidad , Portadores de Fármacos/toxicidad , Lípidos/toxicidad , Fenómenos Magnéticos , Mitocondrias Hepáticas , Nanopartículas/toxicidad , Tamaño de la Partícula , Ratas
18.
Biomater Adv ; 140: 213090, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36027669

RESUMEN

Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bimetallic nanoradiosensitizer, Bi2S3-Fe3O4, to enhance tumor accumulation and promote radiation-induced DNA damage while reducing adverse effects. Due to the presence of both iron oxide and bismuth sulfide metallic nanoparticles in these newly developed nanoparticle, strong radiosensitizing capacity is anticipated through the generation of reactive oxygen species (ROS) to induce DNA damage under X-Ray irradiation. To improve blood circulation time, biocompatibility, colloidal stability, and tuning surface functionalization, the surface of Bi2S3-Fe3O4 bimetallic nanoparticles was coated with bovine serum albumin (BSA). Moreover, to achieve higher cellular uptake and efficient tumor site specificity, folic acid (FA) as a targeting moiety was conjugated onto the bimetallic nanoparticles, termed Bi2S3@BSA-Fe3O4-FA. Biocompatibility, safety, radiation-induced DNA damage by ROS activation and generation, and radiosensitizing ability were confirmed via in vitro and in vivo assays. The administration of Bi2S3@BSA-Fe3O4-FA in 4T1 breast cancer murine model upon X-ray radiation revealed highly effective tumor eradication without causing any mortality or severe toxicity in healthy tissues. These findings offer compelling evidence for the potential capability of Bi2S3@BSA-Fe3O4-FA as an ideal nanoparticle for radiation-induced cancer therapy and open interesting avenues of future research in this area.


Asunto(s)
Neoplasias de la Mama , Nanopartículas del Metal , Fármacos Sensibilizantes a Radiaciones , Animales , Bismuto , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Óxido Ferrosoférrico , Humanos , Nanopartículas del Metal/uso terapéutico , Ratones , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Especies Reactivas de Oxígeno , Albúmina Sérica Bovina/química , Sulfuros
19.
Int J Pharm ; 600: 120479, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33722757

RESUMEN

In the present study, with the aim of improving the permeability of methotrexate (MTX) to the brain, the lipophilic MTX prodrugs containing the ester functional moiety were synthesized. The chemical structure of synthesized prodrugs was characterized and confirmed by FT-IR, NMR and mass spectral studies. Based on the results of in vitro cytotoxic studies, all of the synthesized prodrugs led to decrease in the IC50 in 72 h on U87 cancer cell line and the best result was observed for dihexyl methotrexate (MTX-DH) in comparison with free MTX, which led to decrease the IC50 amount up to 6 folds. In addition, in vivo toxicity on Artemia salina (A. salina) showed that the lipophilic MTX prodrugs have been able to partially mask the toxic profile of free MTX, at the same concentrations. These findings were also in compliance with hemolysis assay results, which confirm that the conjugates has not made the drug more toxic. Furthermore, in vivo study in rat model, was employed to determine the simultaneous drug concentration in brain and plasma. According to the obtained results, the brain-to-plasma concentration ratios (Kp values) of MTX-DH and dioctyl methotrexate (MTX-DO) groups were significantly higher compared with free MTX. Moreover, the uptake clearance of MTX by brain parenchyma increased significantly (3.85 and 9.08-time increased for MTX-DH and MTX-DO prodrugs, respectively). These findings indicate that the synthesized lipophilic MTX prodrugs are non-toxic and able to enhance brain penetration of MTX.


Asunto(s)
Metotrexato , Profármacos , Animales , Encéfalo , Ésteres , Ratas , Espectroscopía Infrarroja por Transformada de Fourier
20.
J Biomater Sci Polym Ed ; 32(3): 320-336, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33026298

RESUMEN

Development of new drugs are confronted with some barriers and challenges, since these projects are mainly expensive, complex, time consuming with lack of success, there is an urgent need to reformulate the current poorly water soluble anti-cancer drugs. In this study, a new type of polymer-curcumin conjugates based on glycidyl azide polymer (GAP) was developed for cancer therapy. The copolymer was used for delivery of curcumin (CUR) as an anticancer drug to cancer cells. Our method is based on the facile conjugation of CUR to amine-containing polymeric vehicles through imine linkage bonds, which could remain stable in normal physiological condition while readily dissociate by an acidic environment and make the prodrug active to liberate its payload CUR to inhibit cell growth. The results demonstrated that fabricated amphiphilic PDCs were self-assembled into nanosized micelles in aqueous solution and the micelles showed an average size of 180 nm with a good polydispersity index. Drug release studies demonstrated that this nano-conjugate is fairly stable at physiologic environments but prone to mild acidic conditions which would trigger the release of conjugated CUR. Moreover, the PDCs micelles exhibited excellent cytotoxicity effect on 4T1 mouse breast cancer cell line but no significant toxicity was observed for the copolymer. In addition, the copolymer did not display remarkable toxicity against A. salina even at high doses of copolymer. In addition, the synthesized PDCs exhibited hemolysis lowers than 6%. The safety of copolymers as a drug vehicle was also confirmed by LD50, since all mice which treated with 5000 mg/Kg (limited dose) were still alive after one week. Our findings revealed that these unique pH-sensitive PDCs may provide a promising approach for delivery of the anticancer drugs to cancer cells.[Formula: see text].


Asunto(s)
Antineoplásicos , Curcumina , Neoplasias , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Curcumina/farmacología , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Ratones , Micelas , Neoplasias/tratamiento farmacológico
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