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1.
ACS Sens ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757734

RESUMO

Due to the current global SARS-CoV-2 pandemic, rapid and accurate diagnostic tools are needed to prevent the spread of COVID-19 across the globe. An electrochemical sensing platform was constructed using CNTs/WO3-screen printed electrodes for imprinting the complete virus particles (SARS-CoV-2 particles) within the polymeric matrix to create viral complementary binding sites. The sensor provided high selectivity toward the target virus over other tested human corona and influenza respiratory interference viruses. The sensitivity performance of the sensor chips was evaluated using different viral concentrations, while the limits of detection and quantification were 57 and 175 pg/mL, respectively. Reaching this satisfied low detection limit (almost 27-fold more sensitive than the RT-PCR), the sensor was applied in clinical specimens obtained from SARS-CoV-2 suspected cases. Thus, dealing directly with clinical samples on the chip could be provided as a portable device for instantaneous and simple point of care in hospitals, airports, and hotspots.

2.
Biomed Pharmacother ; 145: 112376, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34749055

RESUMO

AIM: Doxorubicin/Cyclophosphamide (AC) is one of the standard adjuvant anthracycline-containing regimens that is still in use for breast cancer treatment. Cancer cell resistance and AC-induced side effects make treatment suboptimal and worsen patients' quality of life. This study aimed to improve trans-ferulic acid's (TFA) efficiency via loading into folate-receptor-targeted-poly lactic-co-glycolic acid nanoparticles (FA-PLGA-TFA NPs). Also, investigating both the antitumor efficacy of Doxorubicin (Dox)/FA-PLGA-TFA NPs combination against dimethylbenz[a]anthracene (DMBA)-induced breast cancer and its safety profile. METHODS: FA-PLGA-TFA NPs were optimally fabricated and characterized. Levels of Notch1, Hes1, Wnt-3a, ß-catenin, MMP-9, cyclin D1, Permeability-Glycoprotein (P-gp), ERα, PR, and HER2 were assessed as a measure of the antitumor efficacy of different treatment protocols. Histopathological examination of heart and bone, levels of ALT, AST, ALP, CK-MB, and WBCs count were evaluated to ensure the combination's safety profile. KEY FINDINGS: Dox/FA-PLGA-TFA NPs not only inhibited Notch signaling but also suppressed Notch synergy with Wnt, estrogen, progesterone, and HER2 pathways. Interestingly, Dox/FA-PLGA-TFA NPs decreased P-gp level and preserved heart, bone, and liver health as well as WBCs count. SIGNIFICANCE: Dox/FA-PLGA-TFA NPs reduced the side-effects of each single drug, and at the same time exerted excellent antitumor activity that surpass the AC regimen in evading cancer cell resistance and having a superior safety profile.

3.
Drug Dev Ind Pharm ; : 1-11, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34735303

RESUMO

2-hydroxypropyl-ß-cyclodextrin (HPßCD) nanofiber films have high surface-to-volume ratio and show high dissolution rate of hydrophobic drugs. However, the solubility-enhancement effect of HPßCD films may not be enough to include an effective dose in a sublingually administrable film. Moreover, unmodified HPßCD films are very brittle and difficultly transported and/or handled. So, the addition of polyethylene glycol (PEG) as a plasticizer was suggested to improve their ultimate tensile strength (UTS) and solubilization of hydrophobic drugs. Accordingly, six nanofiber films were developed and characterized, using three molecular weights of PEG (400, 1500 and 6000 Da) with two concentrations each (1:100 and 2:100 PEG:HPßCD), in addition to the unmodified HPßCD nanofibrous film. The results revealed that adding 1:100 of PEG 400 increases the UTS (∼2-fold) and the average fiber diameter (AFD) (∼3-fold). Moreover, the addition of PEG 400 significantly increased the solubility of two hydrophobic model drugs; coumarin (up to 7.7-fold of the original solubility) and 2-nitroimidazole (up to 1.6-fold of the original solubility). However, with higher PEG concentration/molecular weight, both AFD and UTS of the films decreased. On the other hand, it was noted that the solubility of the two model drugs decreased upon using 1500-Da PEG, and then increased with 6000-Da PEG.

4.
Polymers (Basel) ; 13(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34771187

RESUMO

The attempts to explore and optimize the efficiency of diabetic wound healing's promotors are still in progress. Incorporation of cerium oxide nanoparticles (nCeO2) in appropriate nanofibers (NFs) can prolong and maximize their promoting effect for the healing of diabetic wounds, through their sustained releases, as well as the nanofibers role in mimicking of the extra cellular matrix (ECM). The as-prepared nCeO2 were analyzed by using UV-Vis spectroscopy, XRD, SEM-EDX, TEM and FTIR, where TEM and SEM images of both aqueous suspension and powder showed spherical/ovoid-shaped particles. Biodegradable trilayer NFs with cytobiocompatibility were developed to sandwich nCeO2 in PVA NFs as a middle layer where PLA NFs were electrospun as outer bilayer. The nCeO2-loaded trilayer NFs were characterized by SEM, XRD, FTIR and DSC. A two-stage release behavior was observed when the nanoceria was released from the trilayer-based nanofibers; an initial burst release took place, and then it was followed by a sustained release pattern. The mouse embryo fibroblasts, i.e., 3T3 cells, were seeded over the nCeO2-loaded NFs mats to investigate their cyto-biocompatibility. The presence and sustained release of nCeO2 efficiently enhance the adhesion, growth and proliferation of the fibroblasts' populations. Moreover, the incorporation of nCeO2 with a higher amount into the designed trilayer NFs demonstrated a significant improvement in morphological, mechanical, thermal and cyto-biocompatibility properties than lower doses. Overall, the obtained results suggest that designated trilayer nanofibrous membranes would offer a specific approach for the treatment of diabetic wounds through an effective controlled release of nCeO2.

5.
Int J Biol Macromol ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774591

RESUMO

Every year, about 1 out of 9 get burnt in Egypt, with a mortality rate of 37%, and they suffer from physical disfigurement and trauma. For the treatment of second-degree burns, we aim to make a smart bandage provided with control of drug release (chitosan nanoparticles) to enhance the healing process. This bandage is composed of natural materials such as cellulose acetate (CA), chitosan, propolis as the loaded drug (bee resin). Cellulose acetate nanofibers were deacetylated by NaOH after optimizing the reaction time and the concentration of NaOH solution, and the product was confirmed with FTIR analysis. Chitosan/propolis nanoparticles were prepared by ion gelation method with size ranging from 100 to 200 nm and a polydispersity index of 0.3. Chitosan/propolis nanoparticles were preloaded in the CA solution to ensure homogeneity. Loaded deacetylated cellulose nanofibers have shown the greatest hydrophobicity measured by contact angle. Cytotoxicity of propolis and chitosan/propolis nanoparticles were tested and the experimental IC50 value was about 137.5 and 116.0 µg/mL, respectively, with p-value ≤0.001. In addition, chitosan/propolis nanoparticles loaded into cellulose nanofibers showed a cell viability of 89.46%. In-vivo experiments showed that after 21 days of treatment with the loaded nanofibers repairing of epithelial cells, hair follicles and sebaceous glands in the skin of the burn wound were found in a mice model.

6.
Sci Rep ; 11(1): 19808, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615960

RESUMO

In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.

7.
Clin Oral Investig ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34661742

RESUMO

OBJECTIVE: This study aimed to evaluate the regenerative capacity of a newly-developed polycaprolactone (PCL)-based nanofibrous composite scaffold either alone or in combination with adipose-derived mesenchymal stem cells (ADSCs) as a treatment modality for class II furcation defects. MATERIALS AND METHODS: After ADSCs isolation and scaffold characterization, the mandibular premolars of adult male mongrel dogs were selected and randomly assigned into three equal groups. In group I, class II furcation defects were surgically induced to the inter-radicular bone. While class II furcation defects of group II were induced as in group I. In addition, the defects were filled with the prefabricated scaffold. Moreover, class II furcation defects of group III were induced as in group II and instead the defects were filled with the prefabricated scaffold seeded with ADSCs. The dogs were sacrificed at 30 days or at 60 days. Periodontal wound healing/regeneration was evaluated by radiological examination using cone beam computed tomography and histologically using ordinary, histochemical, and immunohistochemical staining. RESULTS: In the two examination periods, group II defects compared to group I, and group III compared to the other groups showed a decrease in defect dimensions radiographically. Histologically, histochemically, and immunohistochemically, they significantly demonstrated better periodontal wound healing/regeneration, predominant collagen type I of newly formed bone and periodontal ligament with a significant increase in the immunoreactivity of vascular endothelial growth factor and osteopontin. CONCLUSIONS: The newly fabricated nanofibrous scaffold has enhanced periodontal wound healing/regeneration of class II furcation defects with further enhancement achieved when ADSCs seeded onto the scaffold before implantation. CLINICAL RELEVANCE: The implementation of our newly-developed PCL-based nanofibrous composite scaffolds in class II furcation defect either alone or in conjunction with ADSCs can be considered as a suitable treatment modality to allow periodontal tissues regeneration.

8.
Biomater Sci ; 9(19): 6609-6622, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582539

RESUMO

Mitochondria are reported to play a paramount role in tumorigenesis which positions them as an instrumental druggable target. However, selective drug delivery to cancer-localized mitochondria remains challenging. Herein, we report for the first time, the design, development and evaluation of a hepatic cancer-specific mitochondria-targeted dual ligated nanoscale metal-organic framework (NMOF) for cellular and mitochondrial sequential drug delivery. Surface functionalization was performed through covalent-linking of folic acid and triphenylphosphonium moieties to the aminated Zr-based MOF, NH2-UiO-66. The characterization of the dual-ligated NMOFs using XRD, FTIR, DSC and BET analysis proved the successful conjugation process. Assessment of the drug loading and release profiling of doxorubicin (DOX)-loaded NMOF confirmed the proper retention of the drug within the NMOF porous structure alongside enhanced release in the tumor acidic environment. Furthermore, biological evaluation of the anti-tumor activity of the DOX-loaded dual-ligated NMOF on hepatocellular carcinoma affirmed the superiority of the developed system in killing the cancerous cells via apoptosis induction and halting cell cycle progression. This study attempts to underscore the promising potential of surface functionalized NMOFs in developing anticancer drug delivery systems to achieve targeted therapy.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Estruturas Metalorgânicas , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Mitocôndrias
9.
Carbohydr Polym ; 270: 118373, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364617

RESUMO

Dual-drug delivery systems were constructed through coaxial techniques, which were convenient for the model drugs used the present work. This study aimed to fabricate core-shell electrospun nanofibrous membranes displaying simultaneous cell proliferation and antibacterial activity. For that purpose, phenytoin (Ph), a well-known proliferative agent, was loaded into a polycaprolactone (PCL) shell membrane, and as-prepared silver-chitosan nanoparticles (Ag-CS NPs), as biocidal agents, were embedded in a polyvinyl alcohol (PVA) core layer. The morphology, chemical composition, mechanical and thermal properties of the nanofibrous membranes were characterized by FESEM/STEM, FTIR and DSC. The coaxial PVA-Ag CS NPs/PCL-Ph nanofibers (NFs) showed more controlled Ph release than PVA/PCL-Ph NFs. There was notable improvement in the morphology, thermal, mechanical, antibacterial properties and cytobiocompatibility of the fibers upon incorporation of Ph and Ag-CS NPs. The proposed core-shell PVA/PCL NFs represent promising scaffolds for tissue regeneration and wound healing by the effective dual delivery of phenytoin and Ag-CS NPs.

10.
Int J Pharm ; 606: 120936, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34310958

RESUMO

HYPOTHESES: Targeted therapy exploits cancerous niches' properties including acidic extracellular environment, hypoxic tumor core, and over expression of tumor-specific surface antigens. The present study aims to develop and evaluate a sequential targeted core-shell nanoparticulate (NPs) system for treatment of breast cancer. Sequential (double-stage) targeting was achieved at the cellular-level through employing the selective CD44- receptor binding hyaluronic acid (HA), followed by subcellular mitochondrial drug-delivery using the mitotropic triphenylphosphonium-conjugated doxorubicin (DOX-TPP+). EXPERIMENTS: NPs were prepared through incorporation of the electrostatic-complexes of DOX.HCl/DOX-TPP+ with tripolyphosphate (STPP-) into chitosan (CS) forming the core that was further coated with HA shell. Physicochemical characterization techniques namely; FTIR, DSC, DLS, morphological evaluation and spectroscopic assessments were implemented. Moreover, the drug entrapment efficiency (EE%), loading capacity (LC%), drug release profile and kinetics were investigated. Lastly, to validate the biological efficiency of the developed NPs, cytotoxic activity was evaluated as well as flow cytometric analyses to assess apoptosis induction and cell-cycle arrest were studied. FINDINGS: Results showed that, the obtained core-shell NPs possessed a spherical shape with a mean size of 220-280 nm and attained high EE% and LC%. In-vitro cytotoxicity evaluations demonstrated successful apoptosis induction and cell-cycle abrogation. Moreover, in-vivo studies on Solid Ehrlich carcinoma (SEC)-bearing mice confirmed the efficient anticancer activity of the mitotropic DOX-TPP+-loaded NPs. Conclusively, the developed core-shell NPs proved efficient in sequential targeting of DOX to breast cancer.


Assuntos
Neoplasias da Mama , Quitosana , Nanopartículas , Animais , Neoplasias da Mama/tratamento farmacológico , Quitosana/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Camundongos
11.
Eur J Pharm Biopharm ; 167: 9-37, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34271117

RESUMO

Hepatocellular carcinoma (HCC) is considered a serious malignancy which affects a large number of people worldwide. Despite the presence of some diagnostic techniques for HCC, the fact that its symptoms somehow overlap with other diseases causes it to be diagnosed at a late stage, hence negatively affecting the prognosis of the disease. The currently available treatment strategies have many shortcomings such as high cost, induction of serious side effects as well as multiple drug resistance, hence resulting in therapeutic failure. Accordingly, nanoformulations have been developed in order to overcome the clinical challenges, enhance the therapeutic efficacy, and elicit chemotherapy tailor-ability. Hybrid nanoparticulate carriers in particular, which are composed of two or more drug vehicles with different physicochemical characteristics combined together in one system, have been recently reported to advance nanotechnology-based therapies. Therefore, this review sheds the light on HCC, and the role of nanotechnology and hybrid nanoparticulate carriers as well as the latest developments in the use of conventional nanoparticles in combating this disease.

12.
Biosens Bioelectron ; 191: 113435, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34175651

RESUMO

Foot-and-mouth disease virus serotype South-Africa territories-2 (FMDV-SAT-2) is the most fastidious known type in Aphthovirus which is subsequently reflected in the diagnosis regime. Rapid and early diagnostic actions are usually taken in response to the FMDV outbreak to prevent the dramatic spread of the disease. Virus imprinted sensor (VIP sensor) is gathering huge attention for the selective detection of pathogens. Thus, the whole virus particles of SAT-2 together with an electropolymerized film of poly(o-phenylenediamine) (PoPD) on gold-copper modified screen-printed electrode were applied to fabricate SAT-2-virus imprinted polymer (SAT-2-VIP). The SAT-2-VIPs were fully characterized using cyclic voltammetry (CV), linear sweep voltammetry (LSV), Atomic force microscopy (AFM), Scanning electron microscope (SEM), and Fourier transform Infra-Red (FTIR) spectroscopy. Excellent selective binding affinity towards the targeted virus particle was achieved with limits of detection and quantification of 0.1 ng/mL and 0.4 ng/mL, respectively. In terms of viral interference, the sensor did not show cross-reactivity towards other animal viruses including FMDV serotype A, O, or even SAT-2 subtype Libya and the un-related virus Lumpy skin disease virus (LSDV). This high selectivity provides a sensible platform with 70 folds more sensitivity than the reference RT-PCR as revealed from the application of SAT-2-VIP sensor for rapid analysis of clinical samples with no need for treatment or equipped labs. Thus, as diagnostic and surveillance technologies, on-site point of care diagnostics for SAT-2 virus are supported.


Assuntos
Técnicas Biossensoriais , Vírus da Febre Aftosa , Febre Aftosa , Animais , Bovinos , Surtos de Doenças , Sorogrupo
13.
Int J Biol Macromol ; 182: 413-424, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798572

RESUMO

Most of the spray products in the market for wound healing applications are loaded with antibiotics that exert their antibacterial effect within the inflammatory stage of wound healing without demonstrating any effect in the subsequent proliferation stage. This study introduces a new aerosolized nanopowder (ANP) formula that not only exhibits antibacterial effect but also antioxidant and enhanced cell proliferation effects. Within the introduced ANP formula, Avicenna marina (Am) extract and neomycin (NM) antibiotic have been loaded within silk-fibroin nanoparticles (FB NPs). The Am has been extracted via different solvent systems, and investigated for its antioxidant and antibacterial activity as well as its ability to enhance cell proliferation. The physicochemical properties, size, zeta-potential and morphology of the prepared Am/FB NPs, NM/FB NPs and ANP formula were investigated. Besides, the ANP formula exhibited good antibacterial activities against Staphylococcus aureus, Methicillin resistant S. aureus, Pseudomonas aeruginosa and Resistant P. aeruginosa. Scratch wound healing assay on human fibroblast monolayers demonstrated 100% wound closure after 24 h upon using the ANP formula as compared to 70% wound closure for positive control (NM). The wound healing ability of the ANP formula has been further confirmed by histopathological evaluation of the wound site and depicted a marked increase in fibroblast proliferation and reduction of inflammatory cells after 15 days with a complete wound closure as compared to controls. The obtained results prove the beneficial effects of the Am extract on wound healing and introduce the developed multitask nanopowder formula as a potential wound healing spray.


Assuntos
Aerossóis/química , Fibroínas/química , Nanopartículas/química , Cicatrização , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular , Proliferação de Células , Liberação Controlada de Fármacos , Epiderme/efeitos dos fármacos , Epiderme/fisiologia , Fibroblastos/efeitos dos fármacos , Humanos , Neomicina/administração & dosagem , Neomicina/farmacologia , Ratos
14.
Carbohydr Polym ; 256: 117498, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33483025

RESUMO

The present work describes the synthesis of a new series of chitosan-gold hybrid nanoparticles (CS-AuNPs) for the delivery of Punicagranatum L. extract (PE). It proposes CS and PE as reducing agents for gold ions in aqueous solution. The effect of PE on the physicochemical properties of the CS-AuNPs was investigated with UV spectroscopy, DLS, DSC, XRD, FTIR, SEM/EDX and TEM. Interestingly, about 50 % reduction in size was observed with using PE alone for gold reduction. The ζ-potential of CS-AuNPs was shifted from +53.1 ± 6.7 mV to 31.0 ± 6.0 mV upon conjugation of the negatively-charged PE polyphenols. The developed PE-conjugated CS-AuNPs exhibited higher stability at different pH values. About 87 % of the loaded PE was released from the NPs over 24 h. The antibacterial activity of CS-PE-AuNPs displayed a synergetic affect against methicillin-resistant S. aureus with MIC and MBC values of 15.6 and 62.5 µg/mL, respectively.


Assuntos
Antibacterianos/farmacologia , Quitosana/química , Farmacorresistência Bacteriana , Ouro/farmacologia , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Romã (Fruta)/química , Carboidratos/química , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Íons , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Tamanho da Partícula , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
15.
J Adv Res ; 28: 51-62, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33364045

RESUMO

Introduction: Guided tissue regeneration (GTR) and guided bone regeneration (GBR) are commonly used surgical procedures for the repair of damaged periodontal tissues. These procedures include the use of a membrane as barrier to prevent soft tissue ingrowth and to create space for slowly regenerating periodontium and bone. Recent approaches involve the use of membranes/scaffolds based on resorbable materials. These materials provide the advantage of dissolving by time without the need of surgical intervention to remove the scaffolds. Objectives: This study aimed at preparing a new series of nanofibrous scaffolds for GTR/GBR applications with enhanced mechanical properties, cell adhesion, biocompatibility and antibacterial properties. Methods: Electrospun nanofibrous scaffolds based on polylactic acid/cellulose acetate (PLA/CA) or poly(caprolactone) (PCL) polymers were prepared and characterized. Different concentrations of green-synthesized silver nanoparticles, AgNPs (1-2% w/v) and hydroxyapatite nanoparticles, HANPs (10-20% w/v) were incorporated into the scaffolds to enhance the antibacterial and bone regeneration activity. Results: In-vitro studies showed that addition of HANPs improved the cell viability by around 50% for both types of nanofibrous scaffolds. The tensile properties were also improved through addition of 10% HANPs but deteriorated upon increasing the concentration to 20%. AgNPs significantly improved the antibacterial activity with 40 mm inhibition zone after 32 days. Additionally, the nanofibrous scaffolds showed a desirable degradation profile with losing around 40-70% of its mass in 8 weeks. Conclusions: The obtained results show that the developed nanofibrous membranes are promising scaffolds for both GTR and GBR applications.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 249: 119301, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33348092

RESUMO

Textile industries produce a massive amount of wastewater that should be cleaned from toxic substances such as fats, colors and any chemicals used during the production steps. Water-treatment methods should be facile, economic, fast and efficient. Here, we report the synthesis, characterization and application of matrix-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) for the removal of anionic dyes from wastewater released from textile industrial plants. The matrix-dispersed SPIONs were synthesized via a solvothermal method in which a polyethyleneimine (PEI) shell was deposited onto SPIONs in order to add positive charges to their surfaces. TEM images revealed that the size of PEI-coated and uncoated SPIONs is 30-50 and 15-30 nm, respectively. Moreover, TEM images depicted that the as synthesized PEI-coated SPIONs show matrix-dispersed structures. Furthermore, the particle size obtained with DLS measurements was found to be 87.93 and 158.9 nm for uncoated and PEI-coated SPIONs, respectively. Bromophenol blue (BPB) and bromocresol green (BCG), two triphenylmethanes, were used as model anionic dyes. FTIR spectroscopy revealed the interaction between the PEI surface coating and the anionic dyes. The apparent ζ-potential measurements showed that the surface negative charges decreased from -13.5 to -4.03 mV upon coating with PEI. In order to investigate the anionic dyes removal/entrapment efficiency of SPIONs, a new derivative visible spectrophotometric method was developed for the simultaneous quantification of BPB and BCG before and after treatment where the linear ranges were 6.98-27.9 and 6.70-26.8 µg/mL and the recovery values were in the ranges of 98.10-101.7% and 99.55-104.8% for BCG and BPB, respectively. It was found that the uptake/adsorption capacity of PEI-coated SPIONs is ca.15.5 and 11.3 mg/g for BCG and BPB, respectively. The calculated thermodynamic parameters for the adsorption of BCG (ΔH = 37.08 J/mol and ΔS = 120.89 J/mol K) and BPB (ΔH = 181.26 J/mol and ΔS = 596.46 J/mol K) and the negative ΔG values indicate that the adsorption is thermodynamically favored. The adsorption processes were found to follow the pseudo-second-order kinetic model with r2 values of 0.9982 and 0.9956 for BCG and BPB, respectively.

17.
Life Sci ; 261: 118458, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32961231

RESUMO

AIM: Niclosamide (NIC) is an anthelmintic agent repurposed as a potent anticancer agent. However, its use is hindered by its poor solubility. We investigated the underlying mechanisms of NIC anticancer activity employing a novel oral NIC pluronic-based nanoformulation and tested its effect in thioacetamide-induced hepatocellular carcinoma (HCC) in rats. We evaluated its antitumor effect through regulating Wnt/ß-catenin and Notch signaling pathways and apoptosis. MAIN METHODS: Niclosamide-loaded pluronic nanoparticles (NIC-NPs) were optimally developed and characterized with sustained release properties up to 7 days. Sixteen weeks after HCC induction, NIC (70 mg/kg) and an equivalent dose of NIC-NPs were administered orally for 3 consecutive weeks. Hepatocyte integrity was assessed by measuring serum levels of aminotransferases, ALP, GGT, bilirubin, albumin and total protein. HCC development was detected by measuring AFP expression. Necroinflammation and fibrosis were scored by histopathological examination. Wnt/ß-catenin and Notch signaling were evaluated by measuring hepatic mRNA levels of Wnt3A, Lrp5 and Lrp6 Co-receptors, Dvl-2, Notch1 and Hes1 and ß-catenin protein levels. Apoptosis was assessed by measuring mRNA and protein levels of cyclin D1 and caspase-3. KEY FINDING: The novel NIC-NPs restored liver integrity, reduced AFP levels and showed improved anticancer and proapoptotic activities compared to drug alone. The inhibitory effect of NIC on Wnt/ß-catenin and Notch signaling pathways was potentiated by the NIC-NPs formulation. SIGNIFICANCE: We conclude that NIC acts by inhibiting Wnt/ß-catenin and Notch signaling and inducing apoptosis in HCC. Developing pluronic-based nanoformulations may be a promising approach to improve NIC solubility and offer the possibility of controlled release.


Assuntos
Anti-Helmínticos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niclosamida/uso terapêutico , Receptores Notch/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Anti-Helmínticos/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Portadores de Fármacos/química , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Micelas , Nanopartículas/química , Niclosamida/administração & dosagem , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
18.
Int J Biol Macromol ; 162: 1760-1769, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32784029

RESUMO

A green synthesis method for gold-chitosan hybrid nanoparticles (Au-CS hNPs) using different concentrations of CS as a capping/reducing agent is reported to investigate the effect of CS concentration on the physicochemical properties as well as the antimicrobial activity of the developed Au-CS hNPs. The as-synthesized Au-CS hNPs were characterized using visible spectrophotometry, FTIR, dynamic light scattering, DSC, XRD, SEM-EDX and TEM. The size of the formed hNPs ranges from 16.9 ± 3.9 nm (highest CS concentration) to 34.7 ± 7.6 nm (lowest CS concentration). It was noticed that increasing the amount of CS increases the ζ-potential from +25.1 to +53.1 mV and enhances the 6-months stability of the produced Au-CS hNPs. Furthermore, the obtained results indicated that the antimicrobial activity, in terms of MIC and CFU assays, is directly proportional to the amount of CS used in the preparation procedure. FTIR analysis revealed that the mechanism of formation of the Au-CS hNPs may involve complexation of CS with Au ions via its NH2 and OH groups followed by the chemical reduction of Au ions to metallic Au NPs. Eventually, higher amounts of CS are necessary for synthesizing highly stable Au-CS hNPs with small size, homogeneous shape and potent antibacterial/antifungal properties.


Assuntos
Antibacterianos , Antifúngicos , Quitosana , Ouro , Nanopartículas Metálicas/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Ouro/química , Ouro/farmacologia , Química Verde , Pseudomonas aeruginosa/efeitos dos fármacos
19.
Carbohydr Polym ; 239: 116201, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32414429

RESUMO

A new series of alginate/chitosan-based nanocomposite microspheres was developed to achieve the maximum health benefit and to minimize the oxidation of omega-3 rich oils (flaxseed or fish oils). The nanocomposite microspheres incorporate curcumin (Cur) as natural antioxidant, and have been prepared using a three-step procedure (oil-in-water (o/w) emulsification, gelation and microencapsulation). The average particle size of Cur-free and Cur-loaded nanocomposites ranged between 139 and 153 nm. The presence of omega-3 rich oils in core of the formulated microspheres was confirmed by XRD and FTIR. Optical microscopy, stereo microscopy, SEM and AFM showed a spherical shape of the microspheres. Microencapsulation efficiency, oxidative stability, release profile of oils as well as the antioxidant and antibacterial activities were investigated. The results suggested that the microspheres could be applied as effective and safe edible vehicles for hydrophobic nutraceuticals like omega-3 rich oils with broad spectrum antibacterial activity.


Assuntos
Alginatos/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Quitosana/química , Sistemas de Liberação de Medicamentos , Ácidos Graxos Ômega-3/farmacologia , Microesferas , Nanocompostos/química , Antibacterianos/química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Portadores de Fármacos/química , Grão Comestível/química , Ácidos Graxos Ômega-3/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oxirredução , Tamanho da Partícula , Picratos/antagonistas & inibidores , Propriedades de Superfície
20.
Int J Biol Macromol ; 155: 772-785, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32234446

RESUMO

Different interpenetrating polymeric networks (IPN) based on sodium alginate, carrageenan and bentonite were developed to remove heavy metals and dyes from contaminated water. Four significant preparation factors; crosslinking time, calcium chloride concentration, alginate to carrageenan mass ratio,and bentonite to carrageenan mass ratio were studied and optimized via full factorial design and response surface methodology to determine the optimum composition with highest adsorption capacity. Different optimal conditions and combinations were found depending on the type of heavy metal or dye to be removed. Low calcium chloride concentration was a common factor in all cases of heavy metals and dyes removal which indicates the negative effect of excessive crosslinking on the removal percentage. The adsorption capacity of methylene blue, Fe3+, Ni2+, and Cr3+ ions is 1271, 1550, 1500 and 1540 mg/g adsorbent, respectively. Reusability tests confirmed that the optimized formulations can be reused five successive times without significant drop in their removal efficiency. Upon utilization of the optimized formulations on real contaminated waters from tannery plant and oasis groundwater, they demonstrated an excellent performance as they removed above 95% of the original heavy metals contaminants and 40% of the acidic dye content.


Assuntos
Alginatos/química , Bentonita/química , Carragenina/química , Metais Pesados/isolamento & purificação , Polímeros/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/normas , Propriedades de Superfície , Purificação da Água/métodos
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