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1.
Int J Nanomedicine ; 15: 4991-5004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764931

RESUMO

Introduction: Various materials and approaches have been used to reduce the mesh-induced inflammatory response and modify the mesh with tissue-matched mechanical properties, aiming to improve the repair of abdominal wall defects. Materials and Methods: In this study, we fabricated a polycaprolactone (PCL)/silk fibroin (SF) mesh integrated with amoxicillin (AMX)-incorporating multiwalled carbon nanotubes (MWCNTs) via electrospinning, grafting and crosslinking, developing a sustainable antibiotic and flexible mesh. AMX was loaded into the hollow tubular MWCNTs by physical adsorption, and a nanofibrous structure was constructed by electrospinning PCL and SF (40:60 w/w). The AMX@MWCNTs were then chemically grafted onto the surfaces of the PCL/SF nanofibers by treating with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) solution for simultaneous crosslinking and coating. The incorporation of AMX into the MWCNTs (AMX@MWCNTs) and the integration of the AMX@MWCNTs with the PCL/SF nanofibers were characterized. Then, the functional mesh was fabricated and fully evaluated in terms of antibacterial activity, mechanical properties and host response. Results: Our results demonstrated that the PCL/SF nanofibrous structure was fabricated successfully by electrospinning. After integrating with AMX@MWCNT by grafting and crosslinking, the functional mesh showed undeformed structure, modified surface hydrophilicity and biocompatible interfaces, abdominal wall-matched mechanical properties, and a sustained-release antibiotic profile in E. coli growth inhibition compared to those of PCL/SF mesh in vitro. In a rat model with subcutaneous implantation, the functional mesh incited less mesh-induced inflammatory and foreign body responses than PCL/SF mesh within 14 days. The histological analysis revealed less infiltration of granulocytes and macrophages during this period, resulting in the loosely packed collagen deposition on the functional mesh and prominent collagen incorporation. Discussion: Therefore, this designed PCL/SF-AMX@MWCNT nanofibrous mesh, functionalized with antibacterial and tissue-matched mechanical properties, provides a promising alternative for the repair of abdominal wall defects.


Assuntos
Amoxicilina/química , Antibacterianos/química , Nanofibras/química , Nanotecnologia/métodos , Telas Cirúrgicas , Amoxicilina/farmacocinética , Amoxicilina/farmacologia , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Colágeno/química , Colágeno/metabolismo , Reagentes para Ligações Cruzadas/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fibroínas/química , Inflamação/etiologia , Masculino , Teste de Materiais , Camundongos , Nanotubos de Carbono/química , Poliésteres/química , Ratos Sprague-Dawley , Telas Cirúrgicas/efeitos adversos
2.
AAPS PharmSciTech ; 21(6): 229, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778976

RESUMO

Lung cancer is the most frequent type of cancer and the leading cause of cancer-related mortality worldwide. This study aimed to develop erlotinib (ELB)-loaded poly(ε-caprolactone) nanocapsules (NCELB) and evaluated their in vitro cytotoxicity in A549 cells. The formulation was characterized in relation to hydrodynamic diameter (171 nm), polydispersity index (0.076), zeta potential (- 8 mV), drug content (0.5 mg.mL-1), encapsulation efficiency (99%), and pH (6.0). NCELB presented higher cytotoxicity than ELB in solution against A549 cells in the MTT and LIVE/DEAD cell viability assays after 24 h of treatment. The main mechanism of cytotoxicity of NCELB was the induction of apoptosis in A549 cells. Further, a significant decrease in A549 colony formation was verified after NCELB treatment in comparison with the unencapsulated drug treatment. The reduction in clonogenic capacity is very relevant as it can reduce the risk of tumor recurrence and metastasis. In conclusion, erlotinib-loaded PCL nanocapsules are promising nanoparticles carriers to increase the efficacy of ELB in lung cancer treatment.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Poliésteres/química , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Cloridrato de Erlotinib/química , Cloridrato de Erlotinib/farmacologia , Humanos , Nanocápsulas/química , Nanopartículas/química
3.
Int J Nanomedicine ; 15: 4899-4918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764924

RESUMO

Purpose: The use of chemotherapeutic agents to combat cancer is accompanied by high toxicity due to their inability to discriminate between cancer and normal cells. Therefore, cancer therapy research has focused on the targeted delivery of drugs to cancer cells. Here, we report an in vitro study of folate-poly(ethylene glycol)-poly(propylene succinate) nanoparticles (FA-PPSu-PEG-NPs) as a vehicle for targeted delivery of the anticancer drug paclitaxel in breast and cervical cancer cell lines. Methods: Paclitaxel-loaded-FA-PPSu-PEG-NPs characterization was performed by in vitro drug release studies and cytotoxicity assays. The NPs cellular uptake and internalization mechanism were monitored by live-cell imaging in different cancer cell lines. Expression of folate receptor-α (FOLR1) was examined in these cell lines, and specific FOLR1-mediated entry of the FA-PPSu-PEG-NPs was investigated by free folic acid competition. Using inhibitors for other endocytic pathways, alternative, non-FOLR1 dependent routes for NPs uptake were also examined. Results: Drug release experiments of Paclitaxel-loaded PPSu-PEG-NPs indicated a prolonged release of Paclitaxel over several days. Cytotoxicity of Paclitaxel-loaded PPSu-PEG-NPs was similar to free drug, as monitored in cancer cell lines. Live imaging of cells treated with either free Paclitaxel or Paclitaxel-loaded PPSu-PEG-NPs demonstrated tubulin-specific cell cycle arrest, with similar kinetics. Folate-conjugated NPs (FA-PPSu-PEG-NPs) targeted the FOLR1 receptor, as shown by free folic acid competition of the FA-PPSu-PEG-NPs cellular uptake in some of the cell lines tested. However, due to the differential expression of FOLR1 in the cancer cell lines, as well as the intrinsic differences between the different endocytic pathways utilized by different cell types, other mechanisms of nanoparticle cellular entry were also used, revealing that dynamin-dependent endocytosis and macropinocytosis pathways mediate, at least partially, cellular entry of the FA-PPSu-PEG NPs. Conclusion: Our data provide evidence that Paclitaxel-loaded-FA-PPSu-PEG-NPs can be used for targeted delivery of the drug, FA-PPSu-PEG-NPs can be used as vehicles for other anticancer drugs and their cellular uptake is mediated through a combination of FOLR1 receptor-specific endocytosis, and macropinocytosis. The exploration of the different cellular uptake mechanisms could improve treatment efficacy or allow a decrease in dosage of anticancer drugs.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Ácido Fólico/química , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Receptor 1 de Folato/metabolismo , Ácido Fólico/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Paclitaxel/química , Paclitaxel/farmacologia
4.
Life Sci ; 258: 118152, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735881

RESUMO

AIMS: Cancer stem cells (CSCs) are the source of tumors and play a key role in the resistance of cancer to therapies. To improve the current therapies against CSCs, in this work we developed a novel system of electrospun polycaprolactone (PCL) nanofibers containing hydroxylated multi-walled carbon nanotubes (MWCNTs-OH) and all-trans retinoic acid (ATRA). MATERIALS AND METHODS: The nanofiber membranes were forged by electrospinning, and the physical and chemical properties of the nanofiber membranes were evaluated by scanning electron microscopy, XRD and Raman etc. The photothermal properties of nanofiber membranes and their effects on CSCs differentiation and cytotoxicity were investigated. Finally, the anti-tumor effect of nanofiber membranes in vivo was evaluated. KEY FINDINGS: The nanofibers formed under optimal conditions were smooth without beads. The nanofibrous membranes with MWCNTs-OH could increase temperature of the medium under near-infrared (NIR) illumination to suppress the viability of glioma stem cells (GSCs). Meanwhile, the added ATRA could further induce the differentiation of GSCs to destroy their stemness and reduce their resistance to heat treatment. Compared with no NIR irradiation, after 2min NIR irradiation, the membranes reduced the in-vitro viability of GSCs by 13.41%, 14.83%, and 26.71% after 1, 2, and 3 days, respectively. After 3 min daily illumination for 3 days, the viability of GSCs was only 22.75%, and similar results were observed in vivo. SIGNIFICANCE: These results showed efficiently cytotoxicity to CSCs by combining heat therapy and differentiation therapy. The nanofiber membranes if inserted at the site after surgical tumor removal, may hinder tumor recurrence.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Glioma/terapia , Nanofibras/uso terapêutico , Células-Tronco Neoplásicas/efeitos dos fármacos , Tretinoína/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Glioma/patologia , Humanos , Hipertermia Induzida/métodos , Masculino , Camundongos Endogâmicos BALB C , Nanofibras/química , Nanotubos de Carbono/química , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Células-Tronco Neoplásicas/patologia , Poliésteres/química , Poliésteres/uso terapêutico , Tretinoína/administração & dosagem
5.
Int J Nanomedicine ; 15: 4151-4169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606670

RESUMO

Purpose: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement. Materials and Methods: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated. Results: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00±0.1717 nm and an APS-loading efficiency of 54.89±2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo. Conclusion: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.


Assuntos
Astrágalo (Planta)/química , Neoplasias da Mama/terapia , Ouro/química , Nanopartículas Multifuncionais/química , Nanotubos/química , Polissacarídeos/química , Terapia por Ultrassom , Animais , Antígenos CD/metabolismo , Apoptose , Morte Celular , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Citocinas/metabolismo , Células Dendríticas/citologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Imunoglobulina G/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Camundongos Endogâmicos BALB C , Fagocitose , Técnicas Fotoacústicas , Poliésteres/síntese química , Poliésteres/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Coelhos , Nanomedicina Teranóstica , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Int J Nanomedicine ; 15: 4591-4606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612358

RESUMO

Objective: Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone which has the ability to treat and activate the CLRN1 pathway to play a pivotal role in hearing loss and hair cell function. To investigate the therapeutic effect of ART in hearing loss induced by gentamicin (GM), an ART-loaded poly(ethylene glycol)-b-poly(ε-caprolactone) mPEG-PCL nanoparticle-based photosensitive hydrogel was developed and tested in this study. Materials and Methods: Artemisinin-loaded mPEG-PCL nanoparticles (mPEG-PCL-ART-NPs) were prepared by a double emulsion method and the formulation was optimized by an orthogonal experimental design. The particle size, zeta potential, morphology and in vitro dissolution of the mPEG-PCL-ART-NPs were well characterized. Biocompatibility of the mPEG-PCL-ART-NPs were tested on HeLa cells with an MTT assay. The photo-crosslinkable biodegradable gelatin methacrylate (GelMA) hydrogel was prepared and its physicochemical properties (such as substitution, photocrosslinking efficiency, cell viability morphology, mechanical and swelling properties) were evaluated. Finally, mPEG-PCL-ART-FITC-NPs, loaded mPEG-PCL-ART-NPs, and loaded mPEG-PCL-ART-NPs-GelMA hydrogels were fabricated and a GM toxicity-induced guinea pig ear damage model was established to determine the effectiveness of the materials on returning auditory function and cochlea pathomorphology. Results: The zeta potential of the mPEG-PCL-ART-NPs was about -38.64 ± 0.21 mV and the average size was 167.51 ± 1.87 nm with an encapsulation efficacy of 81.7 ± 1.46%. In vitro release studies showed that the mPEG-PCL-ART-NPs possessed a sustained-release effect and the MTT experiments showed good biocompatibility properties of the drug-loaded nanoparticles. The results indicated that the 5% GelMA with MA-4% hydrogel had a better crosslinking density and 3D structure for drug loading and drug delivery than controls. Skin penetration results showed that the mPEG-PCL-ART-NPs increased adhesive capacity and avoided fast diffusion in the skin. Most importantly, auditory brainstem response results indicated that the mPEG-PCL-ART-NPs-GelMA hydrogel alleviated hearing loss induced by GM. Conclusion: These results suggested that the presently fabricated mPEG-PCL-ART-NPs-GelMA hydrogels are promising formulations for the treatment of hearing loss induced by GM and lay the foundation for further clinical research of inner ear induction therapy.


Assuntos
Artemisininas/administração & dosagem , Artemisininas/farmacologia , Gentamicinas/efeitos adversos , Perda Auditiva/tratamento farmacológico , Hidrogéis/administração & dosagem , Animais , Artemisininas/farmacocinética , Sistemas de Liberação de Medicamentos , Etilenoglicóis/química , Gelatina , Cobaias , Células HeLa , Perda Auditiva/induzido quimicamente , Humanos , Hidrogéis/química , Metacrilatos/química , Nanopartículas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química
7.
Int J Nanomedicine ; 15: 3903-3920, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606657

RESUMO

Background: Researchers are trying to study the mechanism of neural stem cells (NSCs) differentiation to oligodendrocyte-like cells (OLCs) as well as to enhance the selective differentiation of NSCs to oligodendrocytes. However, the limitation in nerve tissue accessibility to isolate the NSCs as well as their differentiation toward oligodendrocytes is still challenging. Purpose: In the present study, a hybrid polycaprolactone (PCL)-gelatin nanofiber scaffold mimicking the native extracellular matrix and axon morphology to direct the differentiation of bone marrow-derived NSCs to OLCs was introduced. Materials and Methods: In order to achieve a sustained release of T3, this factor was encapsulated within chitosan nanoparticles and chitosan-loaded T3 was incorporated within PCL nanofibers. Polyaniline graphene (PAG) nanocomposite was incorporated within gelatin nanofibers to endow the scaffold with conductive properties, which resemble the conductive behavior of axons. Biodegradation, water contact angle measurements, and scanning electron microscopy (SEM) observations as well as conductivity tests were used to evaluate the properties of the prepared scaffold. The concentration of PAG and T3-loaded chitosan NPs in nanofibers were optimized by examining the proliferation of cultured bone marrow-derived mesenchymal stem cells (BMSCs) on the scaffolds. The differentiation of BMSCs-derived NSCs cultured on the fabricated scaffolds into OLCs was analyzed by evaluating the expression of oligodendrocyte markers using immunofluorescence (ICC), RT-PCR and flowcytometric assays. Results: Incorporating 2% PAG proved to have superior cell support and proliferation while guaranteeing electrical conductivity of 10.8 × 10-5 S/cm. Moreover, the scaffold containing 2% of T3-loaded chitosan NPs was considered to be the most biocompatible samples. Result of ICC, RT-PCR and flow cytometry showed high expression of O4, Olig2, platelet-derived growth factor receptor-alpha (PDGFR-α), O1, myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) high expressed but low expression of glial fibrillary acidic protein (GFAP). Conclusion: Considering surface topography, biocompatibility, electrical conductivity and gene expression, the hybrid PCL/gelatin scaffold with the controlled release of T3 may be considered as a promising candidate to be used as an in vitro model to study patient-derived oligodendrocytes by isolating patient's BMSCs in pathological conditions such as diseases or injuries. Moreover, the resulted oligodendrocytes can be used as a desirable source for transplanting in patients.


Assuntos
Materiais Biomiméticos/farmacologia , Células da Medula Óssea/citologia , Diferenciação Celular , Nanofibras/química , Células-Tronco Neurais/citologia , Oligodendroglia/citologia , Tecidos Suporte/química , Compostos de Anilina/química , Animais , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condutividade Elétrica , Gelatina/química , Grafite/química , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanofibras/ultraestrutura , Células-Tronco Neurais/metabolismo , Oligodendroglia/efeitos dos fármacos , Poliésteres/química , Ratos , Suínos , Tri-Iodotironina/farmacologia
8.
Life Sci ; 257: 118062, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32652138

RESUMO

AIMS: In this study, for the first time, the effect of quercetin (Q) on the characteristic properties, antimicrobial activity, and cell viability of polycaprolactone (PCL)/graphene oxide (GO) electrospun scaffold was investigated. MAIN METHODS: Quercetin loaded graphene oxide nanoparticles have been incorporated into the poly-caprolactone solution, and their mixture has been electrospun to be applied as a nanofibrous scaffold for wound dressing and tissue engineering applications. The properties of scaffolds, like their morphology, tensile strength, hydrophilicity, and in vitro biological performance, are investigated. KEY FINDINGS: The SEM micrographs reveal the uniform bead-free nanofibers with smooth structures have been successfully fabricated via the electrospinning procedure. The overall average of cell viability of NIH/3 T3 fibroblast cells on scaffolds is 95% that means the scaffolds have no toxicity, and FESEM shows cells attach and proliferate on scaffolds. Moreover, among all the fabricated scaffolds, the maximum release of quercetin belongs to PCL/GO/Q 0.5 with about 70% after 15 days, and this scaffold reduces bacterial growth by about 50% after 12 h shows the excellent effect of GO/Q on the antibacterial activity of PCL nanofibers. SIGNIFICANCE: The results confirm that more than 1% of GO has some cytotoxicity, which limits its concentration; therefore, a second antibacterial agent is essential to improve the antibacterial activity of PCL/GO scaffold, and quercetin shows that it is an excellent candidate for this purpose.


Assuntos
Grafite/farmacologia , Poliésteres/química , Quercetina/farmacologia , Tecidos Suporte , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Bandagens , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Grafite/administração & dosagem , Grafite/toxicidade , Camundongos , Células NIH 3T3 , Nanofibras , Quercetina/administração & dosagem , Engenharia Tecidual
9.
PLoS One ; 15(7): e0235893, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692771

RESUMO

Terrestrial nanoplastics (NPs) pose a serious threat to agricultural food production systems due to the potential harm of soil-born micro- and macroorganisms that promote soil fertility and ability of NPs to adsorb onto and penetrate into vegetables and other crops. Very little is known about the dispersion, fate and transport of NPs in soils. This is because of the challenges of analyzing terrestrial NPs by conventional microscopic techniques due to the low concentrations of NPs and absence of optical transparency in these systems. Herein, we investigate the potential utility of small-angle neutron scattering (SANS) and Ultra SANS (USANS) to probe the agglomeration behavior of NPs prepared from polybutyrate adipate terephthalate, a prominent biodegradable plastic used in agricultural mulching, in the presence of vermiculite, an artificial soil. SANS with the contrast matching technique was used to study the aggregation of NPs co-dispersed with vermiculite in aqueous media. We determined the contrast match point for vermiculite was 66% D2O / 33% H2O. At this condition, the signal for vermiculite was ~50-100%-fold lower that obtained using neat H2O or D2O as solvent. According to SANS and USANS, smaller-sized NPs (50 nm) remained dispersed in water and did not undergo size reduction or self-agglomeration, nor formed agglomerates with vermiculite. Larger-sized NPs (300-1000 nm) formed self-agglomerates and agglomerates with vermiculite, demonstrating their significant adhesion with soil. However, employment of convective transport (simulated by ex situ stirring of the slurries prior to SANS and USANS analyses) reduced the self-agglomeration, demonstrating weak NP-NP interactions. Convective transport also led to size reduction of the larger-sized NPs. Therefore, this study demonstrates the potential utility of SANS and USANS with contrast matching technique for investigating behavior of terrestrial NPs in complex soil systems.


Assuntos
Nanoestruturas/análise , Poliésteres/análise , Poluentes do Solo/análise , Solo/química , Nanoestruturas/química , Difração de Nêutrons , Poliésteres/química , Espalhamento a Baixo Ângulo , Poluentes do Solo/química
10.
Life Sci ; 257: 118038, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622947

RESUMO

PURPOSE: The importance of regeneration in large bone defects forces the orthopedic surgeons to search for a proper methodology. The present experiment evaluated the capability of polylactic acid/polycaprolactone/hydroxyapatite (PLA/PCL/HA) scaffold loaded with and without mesenchymal stem cells (MSCs) on bone regeneration. METHODS: Fourier transform infrared spectrometry, X-ray diffraction, scanning electron microscopy, and rheology methodologies were used to characterize the scaffold. Forty Wistar rats were randomly divided into the four groups including the untreated defects as the control group and three other groups in which the bone defects were treated with autologous bones (autograft group), the PLA/PCL/HA scaffolds (PLA/PCL/HA group), and the MSCs-seeded scaffolds (MSCs-seeded PLA/PCL/HA group). RESULTS: Based on the qRT-PCR results, significantly higher expression levels of osteocalcin, osteopontin, and CD31 were seen in the cell-seeded scaffold group compared to the control group (P < 0.05). The CT scanning and radiographic images depicted significantly more newly formed bonny tissue in the MSCs-loaded scaffold and autograft groups than the untreated group (P < 0.001). The immunohistochemistry, biomechanical, histopathologic, and histomorphometric evaluations demonstrated significantly improved regeneration in the autograft and MSCs-loaded scaffold groups compared to the non-treated group (P < 0.05). There were significant differences between the scaffold and untreated groups in all in vivo evaluations (P < 0.05). CONCLUSION: The MSCs enhanced bone healing potential of the PLA/PCL/HA scaffold and the MSCs-seeded scaffold was comparable to the autograft as the golden treatment regimen (P > 0.05).


Assuntos
Regeneração Óssea/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Engenharia Tecidual/métodos , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Durapatita/química , Masculino , Células-Tronco Mesenquimais/fisiologia , Poliésteres/química , Rádio (Anatomia)/metabolismo , Ratos , Ratos Wistar , Tecidos Suporte/química
11.
Food Chem ; 333: 127537, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32683265

RESUMO

Antifungal bioplastic films were developed based on poly(lactic acid) (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) blends as PLA60/PBAT40 (PLA/PBAT) and PBAT60/PLA40 (PBAT/PLA) with incorporated trans-cinnamaldehyde using cast-extrusion. Trans-cinnamaldehyde was more compatible in PLA which exhibited plasticization that increased molecular mobility, crystallinity, permeability but limited volatile release and reduced film strength. Interaction of trans-cinnamaldehyde modified CO functional groups of PLA and PBAT. Phase separation was higher in PBAT/PLA films due to less surface adhesion in PBAT networks. Higher release of trans-cinnamaldehyde enhanced bread crystallinity but gave lower rate of hardness increase due to plasticization of starch and protein and reduced lipid crystallinity. Increased bread hardness correlated with decreased water activity that was effectively prevented by higher release of trans-cinnamaldehyde. Films containing trans-cinnamaldehyde (2-10%) showed high antifungal efficacy against Penicillium sp. and Aspergillus niger but low effective against Rhizopus sp. Trans-cinnamaldehyde reduced bacterial and fungal growth in breads, extending shelf-life for 21 days.


Assuntos
Acroleína/análogos & derivados , Adipatos/química , Alcenos/química , Pão , Embalagem de Alimentos/métodos , Ácidos Ftálicos/química , Poliésteres/química , Acroleína/química , Antifúngicos/química , Pão/microbiologia , Permeabilidade , Amido/química
12.
PLoS One ; 15(6): e0234087, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511282

RESUMO

BACKGROUND: Ventricular septal perforation and left ventricular aneurysm are examples of potentially fatal complications of myocardial infarction. While various artificial materials are used in the repair of these issues, the possibility of associated infection and calcification is non-negligible. Cell-seeded biodegradable tissue-engineered patches may be a potential solution. This study evaluated the feasibility of a new left ventricular patch rat model to study neotissue formation in biodegradable cardiac patches. METHODS: Human induced pluripotent stem cell-derived cardiac progenitor cells (hiPS-CPCs) were cultured onto biodegradable patches composed of polyglycolic acid and a 50:50 poly (l-lactide-co-ε-caprolactone) copolymer for one week. After culturing, patches were implanted into left ventricular walls of male athymic rats. Unseeded controls were also used (n = 10/group). Heart conditions were followed by echocardiography and patches were subsequently explanted at 1, 2, 6, and 9 months post-implantation for histological evaluation. RESULT: Throughout the study, no patches ruptured demonstrating the ability to withstand the high pressure left ventricular system. One month after transplantation, the seeded patch did not stain positive for human nuclei. However, many new blood vessels formed within patches with significantly greater vessels in the seeded group at the 6 month time point. Echocardiography showed no significant difference in left ventricular contraction rate between the two groups. Calcification was found inside patches after 6 months, but there was no significant difference between groups. CONCLUSION: We have developed a surgical method to implant a bioabsorbable scaffold into the left ventricular environment of rats with a high survival rate. Seeded hiPS-CPCs did not differentiate into cardiomyocytes, but the greater number of new blood vessels in seeded patches suggests the presence of cell seeding early in the remodeling process might provide a prolonged effect on neotissue formation. This experiment will contribute to the development of a treatment model for left ventricular failure using iPS cells in the future.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Engenharia Tecidual , Implantes Absorvíveis , Animais , Modelos Animais de Doenças , Ecocardiografia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/transplante , Poliésteres/química , Ácido Poliglicólico/química , Ratos , Ratos Nus , Tecidos Suporte/química , Troponina T/metabolismo , Função Ventricular
13.
Int J Nanomedicine ; 15: 3729-3740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547025

RESUMO

Background: Duraplasty is one of the most critical issues in neurosurgical procedures because the defect of dura matter will cause many complications. Electrospinning can mimic the 3D structure of the natural extracellular matrix whose structure is similar to that of dura matter. Poly(L-lactic acid) (PLLA) has been used to fabricate dura matter substitutes and showed compatibility to dural tissue. However, the mechanical properties of the PLLA substitute cannot match the mechanical properties of the human dura mater. Methods and Results: We prepared stereocomplex nanofiber membranes based on enantiomeric poly(lactic acid) and poly(D-lactic acid)-grafted tetracalcium phosphate via electrospinning. X-ray diffraction results showed the formation of stereocomplex crystallites (SC) in the composite nanofiber membranes. Scanning electron microscope observation images showed that composites nanofibers with higher SC formation can keep its original morphologies after heat treatment, suggesting the heat resistance of composite nanofiber membranes. Differential scanning calorimeter tests confirmed that the melting temperature of composite nanofiber membranes was approximately 222°C, higher than that of PLLA. Tensile testing indicated that the ultimate tensile strength and the elongation break of the stereocomplex nanofiber membranes were close to human dura matter. In vitro cytotoxicity studies proved that the stereocomplex nanofiber membranes were non-toxic. The neuron-like differentiation of marrow stem cells on the stereocomplex nanofiber membranes indicated its neuron compatibility. Conclusion: The stereocomplex nanofiber membranes have the potential to serve as a dura mater substitute.


Assuntos
Materiais Biomiméticos/química , Dura-Máter/fisiologia , Nanofibras/química , Poliésteres/química , Animais , Fosfatos de Cálcio/química , Varredura Diferencial de Calorimetria , Diferenciação Celular , Linhagem Celular , Cristalização , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Nanofibras/ultraestrutura , Neurônios/citologia , Ratos Sprague-Dawley , Estereoisomerismo , Temperatura , Difração de Raios X
14.
Food Chem ; 328: 127131, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32485586

RESUMO

Carvacrol (CAR) is a natural bioactive compound with antioxidant and antimicrobial activity that is present in essential oils. The application of CAR in food preservation is hampered by its high volatility, low solubility in water, and susceptibility to light, heat and oxygen degradation. Polylactide (PLA) is an FDA-approved polymer derived from renewable resources. Controlled release of CAR from PLA nanoparticles (NPs) could improve its antimicrobial efficacy and storage. In this study, negatively charged CAR-NPs and positively charged polyethylenimine (PEI)-coated CAR-(PEI)NPs were formulated by nanoprecipitation methods and characterised by dynamic light scattering, electron microscopy, encapsulation efficiency, and drug loading capacity. The positively charged (PEI)NPs enhanced the in vitro antimicrobial activity of CAR against Escherichia coli, Listeria monocytogenes, Salmonella enterica and Staphylococcus aureus. Bacterial uptake, evaporation tests, release studies and NP stability after storage were assessed to provide evidence supporting CAR-(PEI)NPs as a potential nanocarrier for further development in food preservation.


Assuntos
Antibacterianos/farmacologia , Cimenos/farmacologia , Nanopartículas/química , Poliésteres/química , Antibacterianos/química , Cimenos/química , Cimenos/farmacocinética , Portadores de Fármacos/química , Escherichia coli/efeitos dos fármacos , Microbiologia de Alimentos , Listeria monocytogenes , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Polietilenoimina/química , Salmonella enterica/efeitos dos fármacos , Solubilidade , Staphylococcus aureus/efeitos dos fármacos
15.
Food Chem ; 329: 127165, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32504919

RESUMO

Biogenic amines are the important markers for food spoilage, thus, an on-package sensor for biogenic amine detection is crucial for food quality control. A dual detection platform including colorimetry and LDI-MS was developed for screening and quantitative determining of biogenic amines. Porous PLA film, was fabricated using calcium carbonate nanoparticles to enhance film porosity leading to increased surface area of colorimetric sensor. The color intensity significantly increases depending upon the enhanced analyte concentration with a linear range of 2.0-10.0 mg/mL for putrescine, and 0.1-6.0 mg/mL for cadaverine. On another layer, graphene oxide paper was applied as an LDI-MS substrate for sensitive quantification of biogenic amines. LOD values measured on graphene oxide coated side by LDI-MS were found to be 0.07 pM and 0.02 pM for putrescine and cadaverine, respectively. This platform was successfully applied for the detection of biogenic amines in pork samples with satisfactory results.


Assuntos
Aminas Biogênicas/análise , Colorimetria/métodos , Análise de Alimentos/métodos , Carne de Porco/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Cadaverina/análise , Qualidade dos Alimentos , Grafite , Limite de Detecção , Nanopartículas/química , Poliésteres/química , Porosidade , Putrescina/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação
16.
J Mycol Med ; 30(3): 101003, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32586733

RESUMO

OBJECTIVE: In order to improve the effect of ketoconazole, poly-lactic acid (PLA) nanoparticles containing ketoconazole were prepared, characterized and tested against dermatophytes and Candida spp planktonic and biofilm cells. METHODS: The ketoconazole-PLA nanoparticles obtained by nanoprecipitation were characterized using dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and differential scanning calorimetry. In addition, quantification of encapsulated ketoconazole and the in vitro release profile were determined. Antifungal susceptibility tests against dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum and yeasts Candida albicans, C. dubliniensis, C. krusei, C. parapsilosis, and C. tropicalis were performed. RESULTS: Spherical nanoparticles, with a mean diameter of 188.5nm and an encapsulation efficiency of 45% ketoconazole, were obtained. The nanoparticles containing ketoconazole had superior antifungal activity against all tested fungi strains than free ketoconazole. Inhibition of yeast biofilm formation was also achieved. CONCLUSION: Ketoconazole-PLA nanoparticles resulted in better antifungal activity of ketoconazole nanoparticles than free drug against dermatophytes and Candida species, indicating a promising tool for the development of therapeutic strategies.


Assuntos
Antifúngicos/administração & dosagem , Arthrodermataceae/efeitos dos fármacos , Candida/efeitos dos fármacos , Portadores de Fármacos , Cetoconazol/administração & dosagem , Nanopartículas/química , Poliésteres/química , Antifúngicos/farmacocinética , Arthrodermataceae/fisiologia , Biofilmes/efeitos dos fármacos , Candida/fisiologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Cetoconazol/farmacocinética , Teste de Materiais , Testes de Sensibilidade Microbiana , Resultado do Tratamento
17.
J Vis Exp ; (159)2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32510497

RESUMO

Electrospinning affords researchers the opportunity to fabricate reproducible micro to nanoscale polymer fibers. The 3D fibrous architecture of electrospun polymers is regarded as a structural imitation of the extracellular matrix (ECM). Hence, electrospun fibers fabricated from biocompatible polymers have been widely investigated by tissue engineering researchers for their potential role as an artificial ECM for guiding tissue growth both in vitro and in vivo. All cells are acutely sensitive to their mechanical environment. This has been demonstrated by the discovery of multiple mechanotransduction pathways intrinsically linked to the cytoskeletal actin filaments. The cytoskeleton acts as a mechanical sensor that can direct the functionality and differentiation of the host cell depending on the stiffness and morphology of its substrate. Electrospun fibers can be tuned both in terms of fiber size and morphology to easily modulate the mechanical environment within a fibrous polymer scaffold. Here, methods for electrospinning polycaprolactone (PCL) for three distinct morphologies at two different fiber diameters are described. The morphological fiber categories consist of randomly oriented fibers, aligned fibers, and porous cryogenically spun fibers, with 1 µm and 5 µm diameters. The methods detailed within this study are proposed as a platform for investigating the effect of electrospun fiber architecture on tissue generation. Understanding these effects will allow researchers to optimize the mechanical properties of electrospun fibers and demonstrate the potential of this technology more thoroughly.


Assuntos
Poliésteres/química , Engenharia Tecidual/métodos , Diferenciação Celular , Células Hep G2 , Humanos , Gases em Plasma/química , Porosidade , Esterilização , Resistência à Tração , Tecidos Suporte/química
18.
Chemosphere ; 256: 126985, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32445994

RESUMO

Biodegradable mulch films are an alternative to polyethylene films used in agriculture for weed control, improving crop productivity. This change could minimize the residue production and costs related to the final disposal. Nevertheless, the environmental safety of these biodegradable products is scarcely investigated. In this work, samples of poly(butylene adipate-co-terephthalate)-PBAT mulch films, with and without UV stabilizer additives, were prepared. Aqueous extracts of soil samples, where mulch films were disposed, were investigated using bioassays with Lactuca sativa, Allium cepa, and cell culture HepG2/C3A. As PBAT is expected to suffer photodegradation and biodegradation, soil samples mixed with films before and after these processes were evaluated. Soil aqueous extracts promoted root grown (mainly hypocotyl) of L. sativa, probably due to presence of nutrients. So, to evaluate toxicity potential, in this case it was necessary to use aqueous extract prepared with soil instead of ultrapure water as the control. After doing this analysis it was observed that no adverse impacts due to PBAT films occurred. No chromosomal abnormalities were observed in A. cepa bioassay for any of tested samples. The absence of genotoxic potential was confirmed by comet assay and micronucleus test using human hepatocarcinoma cell line HepG2/C3A. These results showed that the soil did not induce damage to the tested organisms, before and after degradation of PBAT films.


Assuntos
Biodegradação Ambiental , Alface/efeitos dos fármacos , Cebolas/efeitos dos fármacos , Adipatos , Agricultura , Alcenos , Ecotoxicologia , Humanos , Alface/fisiologia , Cebolas/fisiologia , Ácidos Ftálicos , Poliésteres/química , Poluentes do Solo
19.
Int J Nanomedicine ; 15: 2633-2646, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368045

RESUMO

Objective: The aim of this study is to fabricate functional scaffolds to gene delivery bone morphogenetic protein-2 (BMP-2) plasmid for bone formation in bone tissue engineering. Methods: Dendriplexes (DPs) of generation 4 polyamidoamin (G4-PAMAM)/BMP-2 plasmid were prepared through microfluidic (MF) platform. The physiochemical properties and toxicity of DPs were evaluated by DLS, AFM, FESEM and MTT assay. In order to create a suitable environment for stem cell growth and differentiation, poly-l-lactic acid (PLLA) and poly-l-lactic acid/poly (ethylene oxide) (PLLA/PEO) scaffolds containing hydroxyapatite nanoparticles (HA) and DPs were fabricated by the electrospinning method. The osteogenic potency of the scaffolds on human adipose tissue-derived mesenchymal stem cells (hASCs) was investigated. Results: The results revealed that tuning the physical properties of DPs by adjusting flow parameters in microfluidic platform can easily improve the cell viability compared to conventional bulk mixing method. Also, the result showed that the presence of HA and DPs in PLLA/PEO scaffold enhanced alkaline phosphatase (ALP) activity and increased the amount of deposited Ca, as well as, related to osteogenesis gen markers. Conclusion: This study indicated that on using the MF platform in preparation of DPs and loading them along with HA in PLLA/PEO scaffold, the osteogenic differentiation of hASCs could be tuned.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Osso e Ossos/fisiologia , Durapatita/química , Microfluídica , Nanofibras/química , Poliaminas/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Fosfatase Alcalina/metabolismo , Cálcio/metabolismo , Adesão Celular , Morte Celular , Diferenciação Celular , Proliferação de Células , Forma Celular , DNA/metabolismo , Dendrímeros/química , Humanos , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/química , Tamanho da Partícula , Plasmídeos/metabolismo , Poliésteres/química , Resistência à Tração
20.
Chemosphere ; 255: 126901, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32387904

RESUMO

Enhanced nitrate removal from the secondary effluent in municipal wastewater treatment plants (WWTPs) is essential for avoiding water eutrophication. To this end, a vertical baffled solid-phase denitrification reactor (VBSDR) was developed using a starch and polycaprolactone (PCL) blend plate (S-PCL) as a carbon source and biofilm carrier. In this study, we evaluated the denitrification performance and microbial diversity of the VBSDR. The results of the Fourier transform infrared spectroscopy (FTIR), carbon leaching experiment, and scanning electron microscopy (SEM) demonstrated that the S-PCL structure can be attached and degraded more rapidly. Furthermore, the denitrification performance under varied operational conditions, i.e., influent nitrate loading rate (NLR) and operating temperature, was also investigated. Herein, when treating low C/N ratio and low-strength wastewater, a high denitrification rate (DR) [0.33 gN/(L·d)] was achieved. The effect of temperature on DR can be described by the Arrhenius-type equation, which shows that low temperature has a negative influence on DR and nitrate removal efficiency. Furthermore, DR was simultaneously affected by the NLR and temperature. The microbial diversity and community structure were determined by Illumina high-throughput sequencing. The special carbon source led to Acidovorax (denitrifying bacteria) and Flavobacterium (hydrolysis acidifying bacteria) being the VBSDR biofilm's most predominant functional bacteria at the genus level.


Assuntos
Poliésteres/química , Eliminação de Resíduos Líquidos/métodos , Biofilmes , Reatores Biológicos/microbiologia , Carbono/química , Comamonadaceae , Desnitrificação , Nitratos/química , Nitrogênio/química , Amido/química , Temperatura , Águas Residuárias/química
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