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1.
Mater Today Bio ; 23: 100837, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37953758

RESUMEN

The advent of nanotechnology has led to an increased interest in nanocarriers as a drug delivery system that is efficient and safe. There have been many studies addressing nano-scale vesicular systems such as liposomes and niosome is a newer generation of vesicular nanocarriers. The niosomes provide a multilamellar carrier for lipophilic and hydrophilic bioactive substances in the self-assembled vesicle, which are composed of non-ionic surfactants in conjunction with cholesterol or other amphiphilic molecules. These non-ionic surfactant vesicles, simply known as niosomes, can be utilized in a wide variety of technological applications. As an alternative to liposomes, niosomes are considered more chemically and physically stable. The methods for preparing niosomes are more economic. Many reports have discussed niosomes in terms of their physicochemical properties and applications as drug delivery systems. As drug carriers, nano-sized niosomes expand the horizons of pharmacokinetics, decreasing toxicity, enhancing drug solvability and bioavailability. In this review, we review the components and fabrication methods of niosomes, as well as their functionalization, characterization, administration routes, and applications in cancer gene delivery, and natural product delivery. We also discuss the limitations and challenges in the development of niosomes, and provide the future perspective of niosomes.

2.
Biomater Adv ; 149: 213384, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37060635

RESUMEN

Klebsiella pneumoniae (Kp) is a common pathogen inducing catheter-related biofilm infections. Developing effective therapy to overcome antimicrobial resistance (AMR) in Kp is a severe therapeutic challenge that must be solved. This study aimed to prepare niosome-encapsulated GENT (Gentamicin) and EDTA (Ethylenediaminetetraacetic acid) (GENT-EDTA/Nio) to evaluate its efficacy toward Kp strains. The thin-film hydration method was used to prepare various formulations of GENT-EDTA/Nio. Formulations were characterized for their physicochemical characteristics. GENT-EDTA/Nio properties were used for optimization with Design-Expert Software. Molecular docking was utilized to determine the antibacterial activity of GENT. The niosomes displayed a controlled drug release and storage stability of at least 60 days at 4 and 25 °C. GENT-EDTA/Nio performance as antimicrobial agents has been evaluated by employing agar well diffusion method, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) against the Kp bacteria strains. Biofilm formation was investigated after GENT-EDTA/Nio administration through different detection methods, which showed that this formulation reduces biofilm formation. The effect of GENT-EDTA/Nio on the expression of biofilm-related genes (mrkA, ompA, and vzm) was estimated using QRT-PCR. MTT assay was used to evaluate the toxicity effect of niosomal formulations on HFF cells. The present study results indicate that GENT-EDTA/Nio decreases Kp's resistance to antibiotics and increases its antibiotic and anti-biofilm activity and could be helpful as a new approach for drug delivery.


Asunto(s)
Klebsiella pneumoniae , Liposomas , Antibacterianos/farmacología , Antibacterianos/química , Ácido Edético/química , Ácido Edético/farmacología , Klebsiella pneumoniae/genética , Simulación del Acoplamiento Molecular
3.
Int J Biol Macromol ; 230: 123185, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36623618

RESUMEN

This study aims to develop a niosomal platform which can delivery drugs such as tetracycline hydrochloride (TCH) to treat bacterial infections in wounds. To this end, chitosan (CS) was used to obtain a controlled drug release and at the same time antibacterial activity. By design of experiments the niosome encapsulated TCH (TCH-Nio) were optimized for their particle size and encapsulation efficiency, followed by analysis of the release profile of TCH and stability of TCH-Nio and TCH-Nio@CS. The antibacterial activity and cytotoxicity of the fabricated nanoparticles were investigated as well. The release rate of TCH from TCH-Nio@CS in all conditions is less than TCH-Nio. In addition, higher temperature increases the release rate of drug from these formulations. The size, polydispersity index, and encapsulation efficacy of TCH-Nio and TCH-Nio@CS were more stable in 4 °C compared to 25 °C. TCH, TCH-Nio, and TCH-Nio@CS had MIC values of 7.82, 3.91, and 1.95 µg/mL for Escherichia coli, 3.91, 1.95, and 0.98 µg/mL for Pseudomonas aeruginosa, and 1.96, 0.98, and 0.49 µg/mL for Staphylococcus aureus, respectively. Coating of chitosan on niosome encapsulated TCH (TCH-Nio@CS) led to a reduced burst release of TCH from niosome (TCH-Nio), and enabled 2-fold higher antibacterial and anti-biofilm activity against the tested bacterial pathogens E. coli, P. aeruginosa and S. aureus, compared to the uncoated TCH-Nio, and 4-folder higher than the TCH solution, suggesting the synergetic effect of niosome encapsulation and chitosan coating. Moreover, the formulated niosomes displayed no in vitro toxicity toward the human foreskin fibroblast cells (HFF). Both TCH-Nio and TCH-Nio@CS were found to down-regulate the expression of certain biofilm genes, i.e., csgA, ndvB, and icaA in the tested bacteria, which might partially explain the improved antibacterial activity compared to TCH. The obtained results demonstrated that TCH-Nio@CS is capable of controlled drug release, leading to high antibacterial efficacy. The established platform of TCH-Nio@CS enlighten a clinic potential toward the treatment of bacterial infections in skin wounds, dental implants and urinary catheter.


Asunto(s)
Quitosano , Humanos , Quitosano/farmacología , Liposomas/farmacología , Staphylococcus aureus , Liberación de Fármacos , Escherichia coli , Antibacterianos/farmacología , Tetraciclina/farmacología , Cicatrización de Heridas
4.
Int J Nanomedicine ; 17: 6233-6255, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36531115

RESUMEN

Introduction: Breast cancer is among the most prevalent mortal cancers in women worldwide. In the present study, an optimum formulation of letrozole, letrozole-loaded niosome, and empty niosome was developed, and the anticancer effect was assessed in in vitro MCF-7, MCF10A and MDA-MB-231 breast cancer cell lines. Materials and Methods: Various niosomal formulations of letrozole were fabricated through thin-film hydration method and characterized in terms of size, polydispersity index (PDI), morphology, entrapment efficiency (EE%), release kinetics, and stability. Optimized niosomal formulation of letrozole was achieved by response surface methodology (RSM). Antiproliferative activity and the mechanism were assessed by MTT assay, quantitative real-time PCR, and flow cytometry. Furthermore, cellular uptake of optimum formulation was evaluated by confocal electron microscopy. Results: The formulated letrozole had a spherical shape and showed a slow-release profile of the drug after 72 h. The size, PDI, and eEE% of nanoparticles showed higher stability at 4°C compared with 25°C. The drug release from niosomes was in accordance with Korsmeyer-Peppa's kinetic model. Confocal microscopy revealed the localization of drug-loaded niosomes in the cancer cells. MTT assay revealed that all samples exhibited dose-dependent cytotoxicity against breast cancer cells. The IC50 of mixed formulation of letrozole with letrozole-loaded niosome (L + L3) is the lowest value among all prepared formulations. L+L3 influenced the gene expression in the tested breast cancer cell lines by down-regulating the expression of Bcl 2 gene while up-regulating the expression of p53 and Bax genes. The flow cytometry results revealed that L + L3 enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cell lines compared with the letrozole (L), letrozole-loaded niosome (L3), and control sample. Conclusion: Results indicated that niosomes could be a promising drug carrier for the delivery of letrozole to breast cancer cells.


Asunto(s)
Neoplasias de la Mama , Liposomas , Femenino , Humanos , Liposomas/uso terapéutico , Letrozol/farmacología , Letrozol/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Preparaciones de Acción Retardada/uso terapéutico , Células MCF-7
5.
Mater Today Bio ; 16: 100349, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35875198

RESUMEN

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.

6.
Front Pharmacol ; 13: 851242, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35517801

RESUMEN

Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women after lung cancer. The purpose of this study is a targeted delivery toward in vitro (on MCF7 and 4T1 breast cancer cell lines) through niosomes-based nanocarriers. To this end, different bioactive molecules, including hyaluronic acid (HA), folic acid (FA), and polyethylene glycol (PEG), were used and compared for surface modification of niosomes to enhance endocytosis. FA-functionalized niosomes (Nio/5-FU/FA) were able to increase cell cytotoxicity and reduce cell migration and invasion compared to PEG-functionalized niosomes (Nio/5-FU/PEG), and HA-functionalized niosomes (Nio/5-FU/HA) groups in MCF-7 and 4T1 cell lines. Although the Nio/5-FU/PEG and Nio/5-FU/HA demonstrated MCF7 cell uptake, the Nio/5-FU/FA exhibited the most preponderant endocytosis in pH 5.4. Remarkably, in this study 5-FU loaded niosomes (nonionic surfactant-based vesicles) were decorated with various bioactive molecules (FA, PEG, or HA) to compare their ability for breast cancer therapy. The fabricated nanoformulations were readily taken up by breast cancer cells (in vitro) and demonstrated sustained drug release characteristics, inducing cell apoptosis. Overall, the comprehensive comparison between different bioactive molecules-decorated nanoniosomes exhibited promising results in finding the best nano formulated candidates for targeted delivery of drugs for breast cancer therapy.

7.
Iran J Pathol ; 17(2): 183-190, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35463725

RESUMEN

Background & Objective: Breast cancer is the most common cancer among women. One of the most effective treatments for breast cancer is chemotherapy, in which specific drugs destroy the mass and its proliferation is inhibited. Chemotherapy is the most effective adjunctive therapy when multiple medications are used concurrently. Also, combining the drugs with nanocarrier has become an important strategy in targeted therapy. This study is designed to assess the apoptosis induction, cell cycle arrest, and anti-cancer potential of Tamoxifen-Curcumin-loaded niosomes against MCF-7 Cancer Cells. Methods: A novel niosomal formulation of tamoxifen-curcumin with Span 80 and lipid to drug ratio of 20 was employed. The MCF-7 cells were cultured and then treated with IC50 value of tamoxifen-curcumin-loaded niosomes, the combination of tamoxifen and curcumin, tamoxifen, and curcumin alone. Flow cytometry, Real-Time PCR, and cell cycle analysis tests were conducted to evaluate the induction of apoptosis. Results: Drug-loaded niosomes caused up-regulation of bax and p53 genes and down-regulation of bcl2 gene. Flow cytometry studies showed that niosomes containing tamoxifen-curcumin increased apoptosis rate in MCF-7 cells compared to the combination of tamoxifen and curcumin owing to the synergistic effect between the two drugs along with higher cell uptake by formulation niosomal. These results were also confirmed by cell cycle analysis. Conclusion: Co-delivery of curcumin and tamoxifen using optimized niosomal formulation revealed that at acidic pH of MCF-7 cancer cells, released drugs from niosomal carriers would be more effective than physiological pH. This feature of niosomal nanoparticles can reduce the side effects of drugs in normal cells. Niosomal nanoparticles might be used as a biological anti-cancer factor in treatment of breast cancer.

8.
Cancers (Basel) ; 14(7)2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35406569

RESUMEN

An efficient and selective drug delivery vehicle for cancer cells can remarkably improve therapeutic approaches. In this study, we focused on the synthesis and characterization of magnetic Ni1-xCoxFe2O4 nanoparticles (NPs) coated with two layers of methionine and polyethylene glycol to increase the loading capacity and lower toxicity to serve as an efficient drug carrier. Ni1-xCoxFe2O4@Methionine@PEG NPs were synthesized by a reflux method then characterized by FTIR, XRD, FESEM, TEM, and VSM. Naproxen was used as a model drug and its loading and release in the vehicles were evaluated. The results for loading efficiency showed 1 mg of Ni1-xCoxFe2O4@Methionine@PEG NPs could load 0.51 mg of the naproxen. Interestingly, Ni1-xCoxFe2O4@Methionine@PEG showed a gradual release of the drug, achieving a time-release up to 5 days, and demonstrated that a pH 5 release of the drug was about 20% higher than Ni1-xCoxFe2O4@Methionine NPs, which could enhance the intracellular drug release following endocytosis. At pH 7.4, the release of the drug was slower than Ni1-xCoxFe2O4@Methionine NPs; demonstrating the potential to minimize the adverse effects of anticancer drugs on normal tissues. Moreover, naproxen loaded onto the Ni1-xCoxFe2O4@Methionine@PEG NPs for breast cancer cell lines MDA-MB-231 and MCF-7 showed more significant cell death than the free drug, which was measured by an MTT assay. When comparing both cancer cells, we demonstrated that naproxen loaded onto the Ni1-xCoxFe2O4@Methionine@PEG NPs exhibited greater cell death effects on the MCF-7 cells compared with the MDA-MB-231 cells. The results of the hemolysis test also showed good hemocompatibility. The results indicated that the prepared magnetic nanocarrier could be suitable for controlled anticancer drug delivery.

9.
ACS Appl Bio Mater ; 5(4): 1731-1743, 2022 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-35380779

RESUMEN

In the current study, the physicochemical and biological properties of tetracycline-loaded core-shell nanoparticles (Tet/Ni0.5Co0.5Fe2O4/SiO2 and Tet/CoFe2O4/SiO2) were investigated. The antibacterial activity of nanoparticles alone and in combination with tetracycline was investigated against a number of Gram-positive and Gram-negative bacteria for determining minimum inhibitory concentration (MIC) values. The MIC of Tet/Ni0.5Co0.5Fe2O4/SiO2 nanoparticles turned out to be significantly higher than that of Tet/CoFe2O4/SiO2 nanoparticles. Furthermore, Tet/Ni0.5Co0.5Fe2O4/SiO2 nanoparticles exhibited potent antibiofilm activity against pathogenic bacteria compared to Tet/CoFe2O4/SiO2 nanoparticles. The drug delivery potential of both carriers was assessed in vitro up to 124 h at different pH levels and it was found that the drug release rate was increased in acidic conditions. The cytotoxicity of nanoparticles was evaluated against a skin cancer cell line (melanoma A375) and a normal cell line (HFF). Our findings showed that Tet/Ni0.5Co0.5Fe2O4/SiO2 had greater cytotoxicity than CoFe2O4/SiO2 against the A375 cell line, whereas both synthesized nanoparticles had no significant cytotoxic effects on the normal cell line. Nonetheless, the biocompatibility of nanoparticles was assessed in vivo and the interaction of nanoparticles with the kidney was scrutinized up to 14 days. The overall results of the present study implied that the synthesized multifunctional magnetic nanoparticles with drug delivery potential, anticancer activity, and antibacterial activity are promising for biomedical applications.


Asunto(s)
Antineoplásicos , Nanopartículas de Magnetita , Antibacterianos/farmacología , Antineoplásicos/farmacología , Biopelículas , Bacterias Gramnegativas , Bacterias Grampositivas , Nanopartículas de Magnetita/química , Dióxido de Silicio/química , Tetraciclina/farmacología
10.
AAPS PharmSciTech ; 23(1): 57, 2022 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-35048234

RESUMEN

The aim, as proof of concept, was to optimize niosomal formulations of tamoxifen in terms of size, morphology, encapsulation efficiency, and release kinetics for further treatment of the breast cancer (BC). Different assays were carried out to evaluate the pro-apoptotic and cytotoxicity impact of tamoxifen-loaded niosomes in two BC cells, MDA-MB-231 and SKBR3. In this study, tamoxifen was loaded in niosomes after optimization in the formulation. The formulation of niosomes supported maximized drug entrapment and minimized their size. The novel formulation showed improvement in storage stability, and after 60 days only, small changes in size, polydispersity index, and drug entrapment were observed. Besides, a pH-dependent release pattern of formulated niosomes displayed slow release at physiological pH (7.4) and a considerable increase of release at acidic pH (5.4), making them a promising candidate for drug delivery in the BC treatment. The cytotoxicity study exhibited high biocompatibility with MCF10A healthy cells, while remarkable inhibitory effects were observed after treatment of cancerous lines, MDA-MB-231, and SKBR3 cells. The IC50 values for the tamoxifen-loaded niosomes were significantly less than other groups. Moreover, treatment with drug-loaded niosomes significantly changed the gene expression pattern of BC cells. Statistically significant down-regulation of cyclin D, cyclin E, VEGFR-1, MMP-2, and MMP-9 genes and up-regulation of caspase-3 and caspase-9 were observed. These results were in correlation with cell cycle arrest, lessoned migration capacity, and increased caspase activity and apoptosis induction in cancerous cells. Optimization in the formulation of tamoxifen-loaded niosomes can make them a novel candidate for drug delivery in BC treatment.


Asunto(s)
Neoplasias de la Mama , Liposomas , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Puntos de Control del Ciclo Celular , Femenino , Humanos , Tamaño de la Partícula , Tamoxifeno/farmacología
11.
J Drug Target ; 30(5): 476-493, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35060818

RESUMEN

Infection is a disease that is mainly caused by different Gram-negative and Gram-positive bacteria. Treatment of infections requires a considerable amount of antibiotics, which can cause serious damage to the patient's body. Delivering the antibiotic only to the site of infection can prevent these destructive effects, such as the destruction of the normal intestinal flora. The drug delivery system through carriers will take antibiotics into a part of the body involved in the disease. Niosome nanoparticles, which have been made from non-ionic surfactants, have been emerging as ideal drug/antibiotics delivery vehicles. Recently, niosome formulations have been targeted to reduce toxicity and increase accumulation at the target site. Niosomes have performed well in the treatment of local infections, delivery of ocular drugs, and coating of orthopaedic bone/dental implants. This research aimed to highlight the molecular structure and physicochemical properties of niosomes and covered its manufacturing methodologies. Then we critically review the literature on niosomes for the mechanism of drug release, the carrier to deliver antibiotics, and its clinical effectiveness against bacterial infections.


Asunto(s)
Antibacterianos , Liposomas , Antibacterianos/química , Antibacterianos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Humanos , Liposomas/química , Tensoactivos/química
12.
Front Bioeng Biotechnol ; 9: 745099, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34778226

RESUMEN

One of the antibiotics used to treat infections is streptomycin sulfate that inhibits both Gram-negative and -positive bacteria. Nanoparticles are suitable carriers for the direct delivery and release of drug agents to infected locations. Niosomes are one of the new drug delivery systems that have received much attention today due to their excellent biofilm penetration property and controlled release. In this study, niosomes containing streptomycin sulfate were prepared by using the thin layer hydration method and optimized based on the size, polydispersity index (PDI), and encapsulation efficiency (EE%) characteristics. It was found that the Span 60-to-Tween 60 ratio of 1.5 and the surfactant-to-cholesterol ratio of 1.02 led to an optimum formulation with a minimum of size, low PDI, and maximum of EE of 97.8 nm, 0.27, and 86.7%, respectively. The drug release investigation showed that 50.0 ± 1.2% of streptomycin sulfate was released from the niosome in 24 h and reached 66.4 ± 1.3% by the end of 72 h. Two-month stability studies at 25° and 4°C showed more acceptable stability of samples kept at 4°C. Consequently, antimicrobial and anti-biofilm activities of streptomycin sulfate-loaded niosomes against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were found significantly higher than those of free drug, and the minimum inhibitory concentration values decreased 4- to 8-fold. Furthermore, niosome-encapsulated streptomycin up to 1,500 µg/ml exhibited negligible cytotoxicity against the human foreskin fibroblasts cell line, whereas the free drug exhibited slight cytotoxicity at this concentration. Desired physical characteristics and low toxicity of niosomal nano-carriers containing streptomycin sulfate made them a demanded candidate for the treatment of current bacterial infections and biofilms.

13.
Drug Dev Ind Pharm ; 47(9): 1353-1361, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34666567

RESUMEN

High morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made coronavirus disease 2019 (COVID-19) the leading challenge for health experts all over the world. Currently, there is no specific treatment for COVID-19; however, thanks to worldwide intense attempts, novel vaccines such as mRNA-1273 (Moderna TX, Inc.) and BNT162b2 (Biontech/Pfizer) were developed very fast and FDA approved them for emergency use. Nanomedicine-based drug delivery can be an advanced therapeutic strategy to deal with clinical complications of COVID-19. Given the fact that SARS-CoV-2 typically affects the respiratory tract, application of inhalable nanoparticles (NPs) for targeted drug delivery to the alveolar space appears to be an effective and promising therapeutic strategy. Loading the medicinal components into NPs enhances the stability, bioavailability, solubility and sustained release of them. This approach can circumvent major challenges in efficient drug delivery such as solubility and any adverse impact of medicinal components due to off-targeted delivery and resulting systemic complications. Inhalable NPs could be delivered through nasal sprays, inhalers, and nebulizers. NPs also could interfere in virus attachment to host cells and prevent infection. Moreover, nanomedicine-based technologies can facilitate accurate and rapid detection of virus compared to the conventional methods. In this review, the nano-based theranostics modalities for the management of respiratory complications of COVID-19 were discussed.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Vacuna BNT162 , Vacunas contra la COVID-19 , Humanos , Medicina de Precisión , SARS-CoV-2
14.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34360714

RESUMEN

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe2O4 core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe2O4@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe2O4@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/tratamiento farmacológico , Campos Magnéticos , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacología , Femenino , Humanos , Letrozol/química , Letrozol/farmacocinética , Letrozol/farmacología , Liposomas , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Proteínas de Neoplasias/metabolismo
15.
Bioorg Chem ; 115: 105116, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34333420

RESUMEN

In the current study, for the first time, the synergistic activity of curcumin and silver/copper nanoparticles (NPs) was studied against Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, a unique combination of curcumin and silver/copper NPs in free and encapsulated forms was prepared and delivered through a niosomal system. For this purpose, different niosomal formulations of curcumin and metal NPs were prepared by thin film hydration method. Then, the dual drug-loaded niosomes were dispersed in chitosan hydrogel in order to widen its applications. The effect of the molar ratios of lipid to drug and surfactant to cholesterol was investigated to find the optimized noisomal nanoparticles in terms of size, polydispersity index (PDI), and entrapment efficiency (EE). The size and PDI values were measured by dynamic light scattering (DLS). Morphology and in vitro drug release kinetics of niosomes were examined by scanning and transmission electron microscopy (SEM, TEM) and dialysis method, respectively. The drug-loaded niosomes and their hydrogel counterpart were screened for investigating their antibacterial activity against S. aureus and P. aeruginosa by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Furthermore, anti-biofilm assay and expression of biofilm-associated genes by Real-time PCR were performed to evaluate the anti-biofilm effect of NPs. In this study, the drug-loaded niosomal formulations showed good entrapment efficiencies (EE) with a sustained release profile over 72 h. Moreover, compared to free drugs, the optimized niosomal formulations increased antibacterial activity against the bacteria via promotion in the inhibition zone and reduction in MIC and MBC values. Interestingly, gel-based niosomal formulations increased the inhibition zone by about 6 mm and significantly decreased MIC and MBC values compared to niosomal formulations. Also, biofilm eradication of curcumin-metal NPs encapsulated into niosomal hydrogel was highest compared to free and niosomal drugs. Overall, curcumin-Cu or curcumin-Ag nanoparticle loaded niosomes incorporated in hydrogel hold great promise for biomedical applications.


Asunto(s)
Antibacterianos/química , Cobre/química , Curcumina/química , Liposomas/química , Nanopartículas del Metal/química , Plata/química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Curcumina/metabolismo , Curcumina/farmacología , Liberación de Fármacos , Sinergismo Farmacológico , Humanos , Nanopartículas del Metal/toxicidad , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología
16.
Nanomaterials (Basel) ; 11(6)2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34203811

RESUMEN

With the increased occurrence of antibiotic-resistant bacteria, alternatives to classical antibiotics are urgently needed for treatment of various infectious diseases. Medicinal plant extracts are among the promising candidates due to their bioactive components. The aim of this study was to prepare niosome-encapsulated Echinacea angustifolia extract and study its efficacy against multidrug-resistant Klebsiella pneumoniae strains. Encapsulation was first optimized by Design of Experiments, followed by the empirical study. The obtained niosomes were further characterized for the size and morphology using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Spherical niosomes had a diameter of 142.3 ± 5.1 nm, as measured by DLS. The entrapment efficiency (EE%) of E. angustifolia extract reached up to 77.1% ± 0.3%. The prepared niosomes showed a controlled drug release within the tested 72 h and a storage stability of at least 2 months at both 4 and 25 °C. The encapsulated E. angustifolia displayed up to 16-fold higher antibacterial activity against multidrug-resistant K.pneumoniae strains, compared to the free extract. Additionally, the niosome exhibited negligible cytotoxicity against human foreskin fibroblasts. We anticipate that the results presented herein could contribute to the preparation of other plant extracts with improved stability and antibacterial activity, and will help reduce the overuse of antibiotics by controlled release of natural-derived drugs.

17.
Biology (Basel) ; 10(3)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652630

RESUMEN

Cancer is one of the most common causes of mortality, and its various treatment methods can have many challenges for patients. As one of the most widely used cancer treatments, chemotherapy may result in diverse side effects. The lack of targeted drug delivery to tumor tissues can raise the possibility of damage to healthy tissues, with attendant dysfunction. In the present study, an optimum formulation of curcumin-loaded niosomes with a calcium alginate shell (AL-NioC) was developed and optimized by a three-level Box-Behnken design-in terms of dimension and drug loading efficiency. The niosomes were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The as-formulated niosomes showed excellent stability for up to 1 month at 4 °C. Additionally, the niosomal formulation demonstrated a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 3). Cytotoxicity studies showed high compatibility of AL-NioC toward normal MCF10A cells, while significant toxicity was observed in MDA-MB-231 and SKBR3 breast cancer cells. Gene expression studies of the cancer cells showed downregulation of Bcl2, cyclin D, and cyclin E genes, as well as upregulation of P53, Bax, caspase-3, and caspase-9 genes expression following the designed treatment. Flow cytometry studies confirmed a significant enhancement in the apoptosis rate in the presence of AL-NioC in both MDA-MB-231 and SKBR3 cells as compared to other samples. In general, the results of this study demonstrated that-thanks to its biocompatibility toward normal cells-the AL-NioC formulation can efficiently deliver hydrophobic drugs to target cancer cells while reducing side effects.

18.
J Biomed Mater Res A ; 109(6): 966-980, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32865883

RESUMEN

In the current study, niosome-encapsulated tobramycin based on Span 60 and Tween 60 was synthesized and its biological efficacies including anti-bacterial, anti-efflux, and anti-biofilm activities were investigated against multidrug resistant (MDR) clinical strains of Pseudomonas aeruginosa. The niosomal formulations were characterized using scanning electron microscopy, transmission electron microscopy, and dynamic light scattering measurement. The encapsulation efficiency was found to be 69.54% ±; 0.67. The prepared niosomal formulations had a high storage stability to 60 days with small changes in size and drug entrapment, which indicates that it is a suitable candidate for pharmaceutical applications. The results of biological study showed the anti-bacterial activity via reduction of antibiotic resistance, enhanced anti-efflux and anti-biofilm activities by more folds in comparison to free tobramycin. In addition, niosome encapsulated tobramycin down-regulated the MexAB-OprM efflux genes, pslA and pelA biofilm related genes in MDR P. aeruginosa strains. The anti-proliferative activity of formulation was evaluated against HEK293 cell lines, which exhibited negligible cytotoxicity against HEK293 cells. The finding of our study shows that encapsulation of tobramycin in niosome enhanced the antibacterial activity and reduced antibiotic resistance in MDR strains of P. aeruginosa comparing to free tobramycin and it can be considered as a favorable drug delivery system.


Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Liposomas , Pseudomonas aeruginosa/efectos de los fármacos , Tobramicina/administración & dosificación , Tobramicina/farmacología , Biopelículas/efectos de los fármacos , Supervivencia Celular , Regulación hacia Abajo/efectos de los fármacos , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Farmacorresistencia Bacteriana Múltiple/genética , Estabilidad de Medicamentos , Células HEK293 , Humanos , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Pseudomonas aeruginosa/genética
19.
Pharmaceuticals (Basel) ; 15(1)2021 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-35056063

RESUMEN

Breast cancer is one of the most prevalent causes of cancer mortality in women. In order to increase patient prognosis and survival rates, new technologies are urgently required to deliver therapeutics in a more effective and efficient manner. Niosome nanoparticles have been recently employed as therapeutic platforms capable of loading and carrying drugs within their core for both mono and combination therapy. Here, niosome-based nanoscale carriers were investigated as a targeted delivery system for breast cancer therapy. The platform developed consists of niosomes loaded with letrozole and cyclophosphamide (NLC) and surface-functionalized with a folic-acid-targeting moiety (NLCPFA). Drug release from the formulated particles exhibited pH-sensitive properties in which the niosome showed low and high release in physiological and cancerous conditions, respectively. The results revealed a synergic effect in cytotoxicity by co-loading letrozole and cyclophosphamide with an efficacy increment in NLCPFA use in comparison with NLC. The NLCPFA resulted in the greatest drug internalization compared to the non-targeted formulation and the free drug. Additionally, downregulation of cyclin-D, cyclin-E, MMP-2, and MMP-9 and upregulating the expression of caspase-3 and caspase-9 genes were observed more prominently in the nanoformulation (particularly for NLCPFA) compared to the free drug. This exciting data indicated that niosome-based nanocarriers containing letrozole and cyclophosphamide with controlled release could be a promising platform for drug delivery with potential in breast cancer therapy.

20.
Chem Phys Lipids ; 234: 105019, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33232724

RESUMEN

Niosomes, as a kind of drug delivery system, is widely used for the topical delivery of lipophilic drugs. Optimization of niosomes plays an essential role in enhancing their therapeutic efficiencies. This study aims to prepare an optimized niosomal formulation of simvastatin (nSIM), a lipophilic member of statins, through the experiment (Response Surface methodology). Optimized niosomes were characterized in size, polydispersity index (PDI), entrapment efficiency (EE), stability, releasing pattern, and antimicrobial activity. The different molar ratio of surfactant and cholesterol were applied to prepare various formulation of simvastatin loaded niosome. Mean particle size and size distribution were analyzed by dynamic light scattering. Antibacterial activity was determined by MIC and MBC tests against Staphylococcus aureus and Escherichia coli. The release rate of simvastatin from noisome nanoparticles was studied by the Franz diffusion cell method. The release pattern was studied through zero order, first order, Higuchi, Korsmeyer-Peppas, and Hixson-Crowell kinetics models. Optimized niosomes were obtained by span 80, drug to cholesterol ratio of 0.4 with 7 min sonication time. Mean particle size, PDI, zeta potential, and entrapment efficiency (EE%) of optimized nSIM were obtained about 168 nm, 0.34, -32.40, and 96 %, respectively. The niosomes significantly decreased the drug's releasing rate and enhanced antibacterial activity against S. aureus and E. Coli. It was found that the release pattern of drug followed the Higuchi kinetic model which means drug release is by diffusion. Overall, our findings indicated that the prepared simvastatin loaded niosomes showed good stability and biological properties than free drug. Our study suggests that niosomal formulation could be considered as a promising strategy for the delivery of poor water-soluble drugs that enhance antibacterial activity.


Asunto(s)
Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Nanopartículas/química , Simvastatina/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Sistemas de Liberación de Medicamentos , Geles/química , Liposomas/química , Pruebas de Sensibilidad Microbiana , Simvastatina/química
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