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1.
Drug Deliv ; 30(1): 2186312, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36895188

RESUMO

Nano-based drug delivery systems hold significant promise for cancer therapies. Presently, the poor accumulation of drug-carrying nanoparticles in tumors has limited their success. In this study, based on a combination of the paradigms of intravascular and extravascular drug release, an efficient nanosized drug delivery system with programmable size changes is introduced. Drug-loaded smaller nanoparticles (secondary nanoparticles), which are loaded inside larger nanoparticles (primary nanoparticles), are released within the microvascular network due to temperature field resulting from focused ultrasound. This leads to the scale of the drug delivery system decreasing by 7.5 to 150 times. Subsequently, smaller nanoparticles enter the tissue at high transvascular rates and achieve higher accumulation, leading to higher penetration depths. In response to the acidic pH of tumor microenvironment (according to the distribution of oxygen), they begin to release the drug doxorubicin at very slow rates (i.e., sustained release). To predict the performance and distribution of therapeutic agents, a semi-realistic microvascular network is first generated based on a sprouting angiogenesis model and the transport of therapeutic agents is then investigated based on a developed multi-compartment model. The results show that reducing the size of the primary and secondary nanoparticles can lead to higher cell death rate. In addition, tumor growth can be inhibited for a longer time by enhancing the bioavailability of the drug in the extracellular space. The proposed drug delivery system can be very promising in clinical applications. Furthermore, the proposed mathematical model is applicable to broader applications to predict the performance of drug delivery systems.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Sistemas de Liberação de Fármacos por Nanopartículas , Concentração de Íons de Hidrogênio , Liberação Controlada de Fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/farmacologia , Microambiente Tumoral
2.
Carbohydr Polym ; 299: 120230, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36876828

RESUMO

In this study, cellulose acetate (CA)-based nanofiltration membranes, modified with zeolitic imidazole framework-8 (ZIF-8) particles, were prepared with various ZIF-8 contents (0, 0.1, 0.25, 0.5, 1 and 2 wt%), to obtain membranes with improved flux and filtration performance by combining advantages of CA polymer and ZIF-8 metal-organic frameworks. Removal efficiency studies were carried out with bovine serum albumin and two different dyes, along with antifouling performance evaluation. Results of experiments disclosed that as the ZIF-8 ratio increased, the contact angle values decreased. With ZIF-8 addition, the pure water flux of the membranes increased. Besides, the flux recovery ratio value was approximately 85 % for the bare CA membrane, while it increased to above 90 % by blending ZIF-8. Also, in all ZIF-8 doped membranes, a fouling decrease was observed. Importantly, it was observed that the dye removal efficiency increased with the addition of ZIF-8 particles from 95.2 to 97.7 % for Reactive Black 5 dye.

3.
Bioeng Transl Med ; 8(2): e10383, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925674

RESUMO

Tissue engineering (TE) is currently considered a cutting-edge discipline that offers the potential for developing treatments for health conditions that negatively affect the quality of life. This interdisciplinary field typically involves the combination of cells, scaffolds, and appropriate induction factors for the regeneration and repair of damaged tissue. Cell fate decisions, such as survival, proliferation, or differentiation, critically depend on various biochemical and biophysical factors provided by the extracellular environment during developmental, physiological, and pathological processes. Therefore, understanding the mechanisms of action of these factors is critical to accurately mimic the complex architecture of the extracellular environment of living tissues and improve the efficiency of TE approaches. In this review, we recapitulate the effects that biochemical and biophysical induction factors have on various aspects of cell fate. While the role of biochemical factors, such as growth factors, small molecules, extracellular matrix (ECM) components, and cytokines, has been extensively studied in the context of TE applications, it is only recently that we have begun to understand the effects of biophysical signals such as surface topography, mechanical, and electrical signals. These biophysical cues could provide a more robust set of stimuli to manipulate cell signaling pathways during the formation of the engineered tissue. Furthermore, the simultaneous application of different types of signals appears to elicit synergistic responses that are likely to improve functional outcomes, which could help translate results into successful clinical therapies in the future.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36898166

RESUMO

Membrane-based separation processes are part of most water purification plants worldwide. Industrial separation applications, primarily water purification and gas separation, can be improved with novel membranes or modification to existing ones. Atomic layer deposition (ALD) is an emerging technique that is proposed to upgrade certain kinds of membranes independent of their chemistry and morphology. ALD deposits thin, defect-free, angstrom-scale, and uniform coating layers on a substrate's surface by reacting with gaseous precursors. The surface-modifying effects of ALD are described in the present review, followed by a description of various types of inorganic and organic barrier films and how these can be used in combination with ALD. The role of ALD in membrane fabrication and modification is categorized into different membrane-based groups according to the treated medium, i.e., water or gas. In all membrane types, the ALD-based direct deposition of inorganic materials, mainly metal oxides, on the membrane surface can improve antifouling, selectivity, permeability, and hydrophilicity. Therefore, the ALD technique can broaden the applications of membranes to the treatment of emerging contaminants in water and air. Finally, the advancement, limitations, and challenges of ALD-based membrane fabrication and modification are compared to provide a comprehensive guideline for developing next-generation membranes with improved filtration and separation performance.

5.
Nanomaterials (Basel) ; 13(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36770443

RESUMO

Microbes have dominated life on Earth for the past two billion years, despite facing a variety of obstacles. In the 20th century, antibiotics and immunizations brought about these changes. Since then, microorganisms have acquired resistance, and various infectious diseases have been able to avoid being treated with traditionally developed vaccines. Antibiotic resistance and pathogenicity have surpassed antibiotic discovery in terms of importance over the course of the past few decades. These shifts have resulted in tremendous economic and health repercussions across the board for all socioeconomic levels; thus, we require ground-breaking innovations to effectively manage microbial infections and to provide long-term solutions. The pharmaceutical and biotechnology sectors have been radically altered as a result of nanomedicine, and this trend is now spreading to the antibacterial research community. Here, we examine the role that nanomedicine plays in the prevention of microbial infections, including topics such as diagnosis, antimicrobial therapy, pharmaceutical administration, and immunizations, as well as the opportunities and challenges that lie ahead.

6.
Nanomaterials (Basel) ; 12(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35269270

RESUMO

Following the announcement of the outbreak of COVID-19 by the World Health Organization, unprecedented efforts were made by researchers around the world to combat the disease. So far, various methods have been developed to combat this "virus" nano enemy, in close collaboration with the clinical and scientific communities. Nanotechnology based on modifiable engineering materials and useful physicochemical properties has demonstrated several methods in the fight against SARS-CoV-2. Here, based on what has been clarified so far from the life cycle of SARS-CoV-2, through an interdisciplinary perspective based on computational science, engineering, pharmacology, medicine, biology, and virology, the role of nano-tools in the trio of prevention, diagnosis, and treatment is highlighted. The special properties of different nanomaterials have led to their widespread use in the development of personal protective equipment, anti-viral nano-coats, and disinfectants in the fight against SARS-CoV-2 out-body. The development of nano-based vaccines acts as a strong shield in-body. In addition, fast detection with high efficiency of SARS-CoV-2 by nanomaterial-based point-of-care devices is another nanotechnology capability. Finally, nanotechnology can play an effective role as an agents carrier, such as agents for blocking angiotensin-converting enzyme 2 (ACE2) receptors, gene editing agents, and therapeutic agents. As a general conclusion, it can be said that nanoparticles can be widely used in disinfection applications outside in vivo. However, in in vivo applications, although it has provided promising results, it still needs to be evaluated for possible unintended immunotoxicity. Reviews like these can be important documents for future unwanted pandemics.

7.
Mater Today Bio ; 13: 100208, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35198957

RESUMO

Nanotechnology in medical applications, especially in oncology as drug delivery systems, has recently shown promising results. However, although these advances have been promising in the pre-clinical stages, the clinical translation of this technology is challenging. To create drug delivery systems with increased treatment efficacy for clinical translation, the physicochemical characteristics of nanoparticles such as size, shape, elasticity (flexibility/rigidity), surface chemistry, and surface charge can be specified to optimize efficiency for a given application. Consequently, interdisciplinary researchers have focused on producing biocompatible materials, production technologies, or new formulations for efficient loading, and high stability. The effects of design parameters can be studied in vitro, in vivo, or using computational models, with the goal of understanding how they affect nanoparticle biophysics and their interactions with cells. The present review summarizes the advances and technologies in the production and design of cancer nanomedicines to achieve clinical translation and commercialization. We also highlight existing challenges and opportunities in the field.

8.
Ultrasonics ; 123: 106707, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35202978

RESUMO

This work presents an innovative approach according to an experiment-based fitting method to determine the damping property of a viscoelastic coating layer, in a simple, low-cost, and time-effective manner. In this experiment, symmetric and asymmetric ultrasonic Lamb waves were applied to two coated plates with different thicknesses, and the waves were generated using piezo discs. A viscoelastic coating influences the signal amplitude as well as the wave phase. By comparing the amplitude ratio (AR) of the transmitting signals between the coated and bare plates, the damping property of the viscoelastic coating was experimentally determined. Similar to the experiments employing the finite element method (FEM) software, in this experiment, ABAQUS, was employed to verify the conformity between numerical and experimental AR. By selecting a non-dispersive Rayleigh damping ß for the coating layers at all frequencies, the computational cost reduced significantly to one-tenth the original cost. Apart from corroboration by AR matching, the numerical dispersion curves of the group velocity were also validated by experimental curves. The FEM dispersion curves in the frequency range of the tests were found to be highly reliable, with an average error of less than 1% for the first experimental setup and 10% for the second setup. Furthermore, in coated waveguides, the proposed technique could precisely estimate the damping property of the viscoelastic coating layers, where excitability in a wide range of frequencies is required. However, this precision strongly relies on the selected mode, frequency range, PZT quality, and waveguide thickness.

9.
Stem Cell Res Ther ; 12(1): 515, 2021 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565461

RESUMO

Peptic ulcer is one of the most common gastrointestinal tract disorders worldwide, associated with challenges such as refractory morbidity, bleeding, interference with use of anticoagulants, and potential side effects associated with long-term use of proton pump inhibitors. A peptic ulcer is a defect in gastric or duodenal mucosa extending from muscularis mucosa to deeper layers of the stomach wall. In most cases, ulcers respond to standard treatments. However, in some people, peptic ulcer becomes resistant to conventional treatment or recurs after initially successful therapy. Therefore, new and safe treatments, including the use of stem cells, are highly favored for these patients. Adipose-derived mesenchymal stem cells are readily available in large quantities with minimal invasive intervention, and isolation of adipose-derived mesenchymal stromal stem cells (ASC) produces large amounts of stem cells, which are essential for cell-based and restorative therapies. These cells have high flexibility and can differentiate into several types of cells in vitro. This article will investigate the effects and possible mechanisms and signaling pathways of adipose tissue-derived mesenchymal stem cells in patients with refractory peptic ulcers.


Assuntos
Células-Tronco Mesenquimais , Úlcera Péptica , Úlcera Gástrica , Humanos , Úlcera Péptica/terapia , Inibidores da Bomba de Prótons
10.
Infect Genet Evol ; 90: 104773, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33607284

RESUMO

The third pandemic of coronavirus infection, called COVID-19 disease, was first detected in November 2019th. Various determinants of disease progression such as age, sex, virus mutations, comorbidity, lifestyle, host immune response, and genetic background variation have caused clinical variability of COVID-19. The causative agent of COVID-19 is an enveloped coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that invades host cells using an endocytic pathway. The SARS-CoV-2 spike protein is the main viral protein that contributes to the fusion of the virus particle to the host cell through angiotensin-converting enzyme 2 (ACE2). The highly conserved expression of ACE2 is found in various animals, which indicates its pivotal physiological function. The ACE2 has a crucial role in vascular, renal, and myocardial physiology. Genetic factors contributing to the outcome of SARS-CoV-2 infection are unknown; however, variants in the specific sites of ACE2 gene could be regarded as a main genetic risk factor for COVID-19. Given that ACE2 is the main site for virus landing on host cells, the effect of amino acid sequences of ACE2 on host susceptibility to COVID-19 seems reasonable. It would likely have a substantial role in the occurrence of a wide range of clinical symptoms. Several ACE2 variants can affect the protein stability, influencing the interaction between spike protein and ACE2 through imposing conformational changes while some other variants are known to cause a decrease or an increase in the ligand-receptor affinity. The other variations are located at the proteolytic cleavage site, which can influence virus infection; because soluble ACE2 can act as a decoy receptor for virus and decrease virus intake by cell surface ACE2. Notably, polymorphisms of regulatory and non-coding regions such as promoter in ACE2, can play crucial role in different expression levels of ACE2 among different individuals. Many studies should be performed to investigate the involvement of ACE2 polymorphism with susceptibility to COVID-19. Herein, we discuss some reported associations between variants of ACE2 and COVID-19 in details. In addition, the mode of action of ACE2 and its role in SARS-CoV-2 infection are highlighted which is followed by addressing the effects of several ACE2 variants on its protein stability, viral tropism or ligand-receptor affinity, secondary and tertiary structure or protein conformation, proteolytic cleavage site, and finally inter-individual clinical variability in COVID-19. The polymorphisms of regulatory regions of ACE2 and their effect on expression levels of ACE2 are also provided in this review. Such studies can improve the prediction of the affinity of mutant ACE2 variations with spike protein, and help the biopharmaceutical industry to design effective approaches for recombinant hACE2 therapy and vaccination of COVID-19 disease.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , COVID-19/virologia , Suscetibilidade a Doenças , Variação Genética , Interações Hospedeiro-Patógeno , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/diagnóstico , COVID-19/metabolismo , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/metabolismo , Gerenciamento Clínico , Interações Hospedeiro-Patógeno/imunologia , Humanos , Evasão da Resposta Imune , Imunidade Inata , Polimorfismo de Nucleotídeo Único , Prognóstico , Ligação Proteica , Receptores Virais/metabolismo , Índice de Gravidade de Doença
11.
Sensors (Basel) ; 20(24)2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352711

RESUMO

This paper presents a novel single-layer dual band-rejection-filter based on Spoof Surface Plasmon Polaritons (SSPPs). The filter consists of an SSPP-based transmission line, as well as six coupled circular ring resonators (CCRRs) etched among ground planes of the center corrugated strip. These resonators are excited by electric-field of the SSPP structure. The added ground on both sides of the strip yields tighter electromagnetic fields and improves the filter performance at lower frequencies. By removing flaring ground in comparison to prevalent SSPP-based constructions, the total size of the filter is significantly decreased, and mode conversion efficiency at the transition from co-planar waveguide (CPW) to the SSPP line is increased. The proposed filter possesses tunable rejection bandwidth, wide stop bands, and a variety of different parameters to adjust the forbidden bands and the filter's cut-off frequency. To demonstrate the filter tunability, the effect of different elements like number (n), width (WR), radius (RR) of CCRRs, and their distance to the SSPP line (yR) are surveyed. Two forbidden bands, located in the X and K bands, are 8.6-11.2 GHz and 20-21.8 GHz. As the proof-of-concept, the proposed filter was fabricated, and a good agreement between the simulation and experiment results was achieved.

12.
Sensors (Basel) ; 20(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204505

RESUMO

Four state-of-the-art metaheuristic algorithms including the genetic algorithm (GA), particle swarm optimization (PSO), differential evolutionary (DE), and ant colony optimization (ACO) are applied to an adaptive neuro-fuzzy inference system (ANFIS) for spatial prediction of landslide susceptibility in Qazvin Province (Iran). To this end, the landslide inventory map, composed of 199 identified landslides, is divided into training and testing landslides with a 70:30 ratio. To create the spatial database, thirteen landslide conditioning factors are considered within the geographic information system (GIS). Notably, the spatial interaction between the landslides and mentioned conditioning factors is analyzed by means of frequency ratio (FR) theory. After the optimization process, it was shown that the DE-based model reaches the best response more quickly than other ensembles. The landslide susceptibility maps were developed, and the accuracy of the models was evaluated by a ranking system, based on the calculated area under the receiving operating characteristic curve (AUROC), mean absolute error, and mean square error (MSE) accuracy indices. According to the results, the GA-ANFIS with a total ranking score (TRS) = 24 presented the most accurate prediction, followed by PSO-ANFIS (TRS = 17), DE-ANFIS (TRS = 13), and ACO-ANFIS (TRS = 6). Due to the excellent results of this research, the developed landslide susceptibility maps can be applied for future planning and decision making of the related area.

13.
J Environ Manage ; 260: 109867, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32090793

RESUMO

Forests are important dynamic systems which are widely affected by fire worldwide. Due to the complexity and non-linearity of the forest fire problem, employing hybrid evolutionary algorithms is a logical task to achieve a reliable approximation of this environmental threat. Three fuzzy-metaheuristic ensembles, based on adaptive neuro-fuzzy inference systems (ANFIS) incorporated with genetic algorithm (GA), particle swarm optimization (PSO), and differential evolution (DE) evolutionary algorithms are used to produce the forest fire susceptibility map (FFSM) of a fire-prone region in Iran. A sensitivity analysis is also executed to evaluate the effectiveness of the proposed ensembles in terms of time and complexity. The results revealed that all models produce FFSMs with acceptable accuracy. However, the superiority of the GA-ANFIS was shown in both recognizing the pattern (AUROCtrain = 0.912 and Error = 0.1277) and predicting unseen fire events (AUROCtest = 0.850 and Error = 0.1638). The optimized structures of the proposed GA-ANFIS and PSO-ANFIS ensembles could be good alternatives to traditional forest fire predictive models, and their FFSMs can be promisingly used for future planning and decision making in the proposed area.


Assuntos
Incêndios Florestais , Algoritmos , Lógica Fuzzy , Irã (Geográfico)
14.
Adv Pharm Bull ; 10(1): 39-45, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32002360

RESUMO

Purpose: Hydroxyurea (HU) is a well-known chemotherapy drug with several side effects which limit its clinical application. This study was conducted to improve its therapeutic efficiency against breast cancer using liposomes as FDA-approved drug carriers. Methods: PEGylated nanoliposomes-containing HU (NL-HU) were made via a thin-film hydration method, and assessed in terms of zeta potential, size, morphology, release, stability, cellular uptake, and cytotoxicity. The particle size and zeta potential of NL-HU were specified by zeta-sizer. The drug release from liposomes was assessed by dialysis diffusion method. Cellular uptake was evaluated by flow cytometry. The cytotoxicity was designated by methyl thiazolyl diphenyl-tetrazolium bromide (MTT) test. Results: The size and zeta value of NL-HU were gotten as 85 nm and -27 mV, respectively. NL-HU were spherical.NL-HU vesicles were detected to be stable for two months. The slow drug release and Weibull kinetic model were obtained. Liposomes considerably enhanced the uptake of HU into BT-474 human breast cancer cells. The cytotoxicity of NL-HU on BT-474 cells was found to be significantly more than that of free HU. Conclusion: The results confirmed these PEGylated nanoliposomes containing drug are potentially suitable against in vitro model of breast cancer.

15.
Acta Biomed ; 89(3): 378-381, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30333462

RESUMO

BACKGROUND AND AIM: Applying fractional flow reserve (FFR) recently helped to assess borderline coronary defects and also facilitates assessment of these lesions. The present study aimed to assess cost-effectiveness of FFR in detection of these borderline lesions. METHODS: This cross-sectional study was conducted on140 consecutive patients with 219 diseased arteries who underwent coronary angiography and suffered intermediate coronary lesions. RESULTS: Of 18 patients who candidate for CABG before FFR, only one patient underwent CABG after determining FFR (P-value<0.05), while 15 patients were scheduled for PCI and 2 patients for medical treatment. Of 122 patients who candidate for PCI, 59 were programmed to underwent PCI after FFR determination(P-value<0.05), while the strategy in 63 patients (47 with one-vessel disease, 15 with two vessel diseases, and 1 with three vessel diseases) was modified to medical treatment. Considering strategy modifying from PCI to medical treatment, 101 stents were saved (P-value<0.05). Also, in change of strategy from CABG to PCI, spending has decreased as much as 77.3% (P-value<0.05). Furthermore, the change of treatment approach from PCI on much number of coronary vessels to PCI on less number of coronary lesions led to saving of 52.2% of costs(P-value<0.05). CONCLUSIONS: In patients with an intermediate coronary lesion, measuring FFR to guide the decision to determine treatment strategy may lead to significant cost savings.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico , Adulto , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/uso terapêutico , Tomada de Decisão Clínica , Ponte de Artéria Coronária , Doença da Artéria Coronariana/economia , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/terapia , Redução de Custos , Análise Custo-Benefício , Estudos Transversais , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Projetos Piloto , Índice de Gravidade de Doença , Fumar/epidemiologia
16.
Appl Opt ; 57(14): 3693-3703, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29791329

RESUMO

Because of exhibiting extraordinary features, metamaterial absorbers have captured considerable attention in recent years, especially at visible frequencies. In this paper, a new design of a metamaterial-inspired perfect visible absorber (MIPVA) is investigated, which exhibits ultra-broadband, polarization-independent, and wide-angle performances. The proposed MIPVA provides a flat and near unity absorbance (>99%) in an ultra-broad range of radiation wavelengths from λ=500 to 625 nm, while retaining its convincing absorptivity over the entire visible wavelengths. A comprehensive parametric study is accomplished to demonstrate the effects of structural parameters on the absorptivity of the designed MIPVA. To clarify the physical mechanism of absorption, the electric field and surface current distributions of MIPVA are also monitored and elaborately discussed throughout the paper. The results show that the proposed MIPVA exhibits a polarization-insensitive absorption behavior in a wide range of incident wave angles. The interference theory is also utilized to verify the results. In addition, our MIPVA has a compact and low-profile design, while its ability to absorb solar radiation is significantly improved with respect to preceding studies in terms of both the frequency bandwidth and absorptivity; thereby, it is a worthy candidate to play an essential role in different visible-range applications.

17.
Artif Cells Nanomed Biotechnol ; 46(4): 757-763, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28643525

RESUMO

Targeted drug delivery has received considerable attention due to its key role in improving therapeutic efficacy and reducing the side effects of anticancer drugs. Bleomycin (BLM) is an anticancer antibiotic with short half-life, low therapeutic and high side effects that limit its clinical applications. This study aims to evaluate the anticancer potential of folate-targeted liposomal bleomycin (FL-BLM) and its free-folate form (L-BLM) on two different cancer cell lines including human cervix carcinoma HeLa, and human breast carcinoma MCF-7 cells. Furthermore, the effect of FL-BLM in induction of apoptosis and cell cycle arrest was studied by flow cytometry. FL-BLM was prepared by thin film hydration method and folic acid was conjugated to nanoliposomes by post insertion technique. Anticancer activity was evaluated by MTT assay. The cytotoxicity of FL-BLM against HeLa cells was significantly increased compared to L-BLM and conventional BLM. Flow cytometry and annexin-V analysis indicated that FL-BLM effectively induced apoptosis and cell-cycle arrest in HeLa cells especially at G2/M phase. In addition, the uptake of FL-BLM by Hela cells was significantly increased as compared to the MCF-7 cells. Overall, our findings indicated that FL-BLM may be promising formulation for targeted drug delivery to folate receptor-positive tumour cells.


Assuntos
Bleomicina , Ácido Fólico , Nanopartículas , Neoplasias/tratamento farmacológico , Bleomicina/química , Bleomicina/farmacocinética , Bleomicina/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacocinética , Ácido Fólico/farmacologia , Células HeLa , Humanos , Lipossomos , Células MCF-7 , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia
18.
Chem Biol Drug Des ; 90(5): 953-961, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28498511

RESUMO

Folate receptor (FR)-mediated drug delivery is a promising approach for active targeting of drugs to the FR-positive tumor cells. Bleomycin (BLM) is an antitumor antibiotic with poor therapeutic activity as a result of its limited diffusion into tumor cells. The aim of this study was to investigate whether FR-targeted PEGylated nanoliposomes (FPNL) can effectively deliver BLM to tumor cells and enhance its in vitro and in vivo efficacy. FPNL and PNL (non-targeted) were prepared by thin film hydration method, and their physiochemical properties, cellular uptake, tissue distribution and tumor inhibitory effects were investigated. In Lewis lung cancer (LLC1) cells, FPNL containing BLM showed 2.38-fold and 3.26-fold higher cytotoxicity compared to PNL-BLM and free BLM, respectively. Moreover, the uptake of FPNL by these cells was increased as compared to the PNL. Furthermore, FPNL showed significantly higher tumor distribution of BLM in the LLC1 cells and more tumor inhibition efficacy compared to free BLM and PNL. Both formulations of nanoliposomes had longer plasma half-life than that of free BLM. Therefore, FPNL may be suitable carriers for targeted drug delivery to FR-positive tumor cells.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Bleomicina/farmacocinética , Bleomicina/farmacologia , Bleomicina/uso terapêutico , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular Tumoral , Feminino , Receptores de Folato com Âncoras de GPI/metabolismo , Humanos , Lipossomos , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo , Neoplasias/patologia
19.
Chem Biol Drug Des ; 89(4): 492-497, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27637429

RESUMO

Bleomycin is an anticancer drug used against various types of cancers. The aim of this study was to prepare a new PEGylated and non-PEGylated nanoliposomal formulation of bleomycin (PEG-nLip-BLM and nLip-BLM) and evaluate their anticancer activity in different tumor cell lines. The liposomes were prepared by thin-film hydration method, and then, bleomycin (BLM) was loaded to the prepared vesicles. The size, zeta potential, entrapment efficiency, loading rate, release profile, and cytotoxicity of liposomal formulations in TC-1, LLC1, and HFLF-PI5 cell lines were investigated. Mean particle size and zeta potential of the PEG-nLip-BLM and nLip-BLM were found to be 99.4 ± 4.6 nm and -34.83 ± 4.7 mV; and 112.2 ± 7.2 nm and -27.5 ± 3.2 mV, respectively, which were stable for at least 2 months. Encapsulation and loading efficiency of BLM for PEG-nLip-BLM and nLip-BLM were obtained about 83.1 ± 4.2% and 14.3 ± 2.5%; and 78.3 ± 8.6% and 11.1 ± 3.3%, respectively. Drug release study showed a slow release pattern without considerable burst effect. The liposomal formulations indicated lower toxicity compared to free drug in case of TC-1 and HFLF-PI5 cells, but their cytotoxicity against LLC1 cells was significantly higher than free drug. The results of this study indicated that PEG-nLip-BLM can be a suitable candidate for drug delivery to solid tumors.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Bleomicina/farmacologia , Lipossomos , Nanoestruturas , Animais , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Camundongos , Microscopia Eletrônica de Varredura
20.
Turk J Med Sci ; 45(4): 794-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26422848

RESUMO

BACKGROUND/AIM: House flies (Musca domestica) are of major public health concern in areas with poor sanitation and hygiene conditions. Biological control through the use of parasitoids and pathogens is one of the alternatives to the use of chemical pesticides for control of insects of public health importance. MATERIALS AND METHODS: The effects of the delta endotoxin of Bacillus thuringiensis on house fly larval mortality were studied. Gel filtration and SDS-PAGE methods were used for separation and purification of proteins. Delta endotoxin was incubated with larvae in concentrations of 0.43 mg/mL and 0.27 mg/mL in bioassay tests. RESULTS: The results of this study indicated protein crystal toxicity against larvae of the house fly. A concentration of 0.43 mg/mL of this toxin caused 100% mortality in house fly larvae. The LD50 amount of these toxins was calculated as 125 µg/g. CONCLUSION: The results of this study suggest that the use of the protein crystal including delta endotoxin of Bacillus thuringiensis serotype H14 is an effective weapon in the biological fight against the house fly.


Assuntos
Bacillus thuringiensis , Toxinas Bacterianas , Endotoxinas , Moscas Domésticas , Inseticidas , Larva/efeitos dos fármacos , Animais , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Toxinas Bacterianas/isolamento & purificação , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidade , Eletroforese em Gel de Poliacrilamida/métodos , Endotoxinas/isolamento & purificação , Endotoxinas/metabolismo , Endotoxinas/toxicidade , Moscas Domésticas/efeitos dos fármacos , Moscas Domésticas/fisiologia , Inseticidas/química , Inseticidas/farmacologia , Controle Biológico de Vetores/métodos , Sorogrupo
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