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1.
Sci Total Environ ; 873: 162438, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36842591

RESUMO

The complication of stent implantation is the biggest obstacle to the success of its clinical application. In this study, we developed a combination way of 3D printing and the coating technique for preparation of functional polyurethane stents against stent implantation-induced thrombosis and postoperative infection. SEM, XPS, static water contact angle, and XRD demonstrated that the functional polyurethane stent had a 37 µm-thickness membrane composed of zein nanospheres (250-350 nm). Meanwhile, ZnO nanoparticles were encapsulated in zein nanospheres while heparin was adsorbed on the surface, causing 97.1 ± 6.4 % release of heparin in 120 min (first-order kinetic model) and 62.7 ± 5.6 % release of Zn2+ in 9 days (Korsmeyer-Peppas model). The mechanical analysis revealed that the functional polyurethane stents had about 8.61 MPa and 2.5 MPa tensile strength and bending strength, respectively. The in vitro biological analysis showed that the functional polyurethane stents had good EA.hy926 cells compatibility (97.9 ± 3.8 %), anti-coagulation response (comparable plasma protein, platelet adhesion and suppressed clotting) and sustained antibacterial activities by comparison with the bare polyurethane stent. The preliminary evaluation by rabbit ex vivo carotid artery intervention experiment demonstrated that the functional polyurethane stents could maintain blood circulation under the continuous stresses of blood flow. Meanwhile, the detailed data from the simulated implant infection experiment in vivo showed the functional polyurethane stents could effectively reduce microbial infection by 3-6 times lower and improve fibrosis and macrophage infiltration.


Assuntos
Nanosferas , Trombose , Zeína , Animais , Coelhos , Poliuretanos , Nanosferas/efeitos adversos , Trombose/etiologia , Heparina/farmacologia , Stents/efeitos adversos
2.
Nanomedicine (Lond) ; 13(19): 2377-2395, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30346255

RESUMO

AIM: Lactoferrin (LF)-targeted gliadin nanoparticles (GL-NPs) were developed for targeted oral therapy of hepatocellular carcinoma. MATERIALS & METHODS: Celecoxib and diosmin were incorporated in the hydrophobic matrix of GL-NPs whose surface was decorated with LF by electrostatic interaction for binding to asialoglycoprotein receptors overexpressed by liver cancer cells. RESULTS: Targeted GL-NPs showed enhanced cytotoxic activity and increased cellular uptake in liver tumor cells compared with nontargeted NPs. Moreover, they demonstrated superior in vivo antitumor effects including reduction in the expression levels of tumor biomarkers and induction of caspase-mediated apoptosis. Ex vivo imaging of isolated organs exhibited extensive accumulation of NPs in livers more than other organs. CONCLUSION: LF-targeted GL-NPs could be considered as an efficient nanoplatform for targeted oral drug delivery for liver cancer therapy.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/administração & dosagem , Fitoterapia , Administração Oral , Animais , Carcinoma Hepatocelular/patologia , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Células Hep G2 , Humanos , Lactoferrina/química , Neoplasias Hepáticas/patologia , Camundongos , Nanopartículas/química , Nanosferas/administração & dosagem , Nanosferas/efeitos adversos , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Small ; 12(26): 3510-5, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27191183

RESUMO

Hollow and non-hollow mesoporous silica nanospheres are synthesized and used for cancer vaccine adjuvants. The hollow structure of mesoporous silica nanospheres significantly promote cellular uptake of a model cancer antigen by macrophage-like cells in vitro, improve anti-cancer immunity, CD4(+) and CD8(+) T cell populations in splenocytes of mice in vivo.


Assuntos
Adjuvantes Imunológicos/química , Nanosferas/química , Dióxido de Silício/química , Adjuvantes Imunológicos/efeitos adversos , Animais , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/química , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Microscopia Eletroquímica de Varredura , Microscopia Eletrônica de Transmissão , Células NIH 3T3 , Nanosferas/efeitos adversos , Nanosferas/ultraestrutura , Porosidade
4.
Eur J Pharm Biopharm ; 96: 396-408, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26386355

RESUMO

A polymer based material was developed to act as an embolic agent and drug reservoir for the treatment of arteriovenous malformations (AVM) and hyper vascularized solid tumors. The aim was to combine the blocking of blood supply to the target region and the inhibition of the embolization-stimulated angiogenesis. The material is composed of an ethanolic solution of a linear acrylate based copolymer and acrylate calibrated microparticles containing nanospheres loaded with sunitinib, an anti-angiogenic agent. The precipitation of the linear copolymer in aqueous environment after injection through microcatheter results in the formation of an in-situ embolization gel whereas the microparticles serve to increase the cohesive properties of the embolization agent and to form a reservoir from which the sunitinib-loaded nanospheres are released post-embolization. The swollen state of the microparticles in contact with aqueous medium results in the release of the nanospheres out of microparticles macromolecular structure. After the synthesis, the formulation and the characterization of the different components of the material, anti-angiogenic activity was evaluated in vitro using endothelial cells and in vivo using corneal neovascularization model in rabbit. The efficiency of the arterial embolization was tested in vivo in a sheep model. Results proved the feasibility of this new system for vascular embolization in association with an in situ delivery of anti-angiogenic drug. This combination is a promising strategy for the management of arteriovenous malformations and solid tumors.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Sistemas de Liberação de Medicamentos , Embolização Terapêutica , Endotélio Vascular/efeitos dos fármacos , Indóis/administração & dosagem , Nanosferas/química , Neovascularização Patológica/prevenção & controle , Pirróis/administração & dosagem , Acrilatos/efeitos adversos , Acrilatos/química , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Malformações Arteriovenosas/tratamento farmacológico , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Córnea/irrigação sanguínea , Córnea/efeitos dos fármacos , Córnea/patologia , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/efeitos adversos , Embolização Terapêutica/efeitos adversos , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Géis , Células Endoteliais da Veia Umbilical Humana/citologia , Indóis/efeitos adversos , Indóis/farmacologia , Indóis/uso terapêutico , Músculos Intercostais/irrigação sanguínea , Músculos Intercostais/efeitos dos fármacos , Músculos Intercostais/patologia , Nanosferas/efeitos adversos , Neovascularização Patológica/patologia , Pirróis/efeitos adversos , Pirróis/farmacologia , Pirróis/uso terapêutico , Coelhos , Distribuição Aleatória , Carneiro Doméstico , Sunitinibe
5.
Proc Natl Acad Sci U S A ; 112(34): 10669-72, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26240350

RESUMO

Paleoanthropologists and vertebrate paleontologists have for decades debated the etiology of tooth wear and its implications for understanding the diets of human ancestors and other extinct mammals. The debate has recently taken a twist, calling into question the efficacy of dental microwear to reveal diet. Some argue that endogenous abrasives in plants (opal phytoliths) are too soft to abrade enamel, and that tooth wear is caused principally by exogenous quartz grit on food. If so, variation in microwear among fossil species may relate more to habitat than diet. This has important implications for paleobiologists because microwear is a common proxy for diets of fossil species. Here we reexamine the notion that particles softer than enamel (e.g., silica phytoliths) do not wear teeth. We scored human enamel using a microfabrication instrument fitted with soft particles (aluminum and brass spheres) and an atomic force microscope (AFM) fitted with silica particles under fixed normal loads, sliding speeds, and spans. Resulting damage was measured by AFM, and morphology and composition of debris were determined by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Enamel chips removed from the surface demonstrate that softer particles produce wear under conditions mimicking chewing. Previous models posited that such particles rub enamel and create ridges alongside indentations without tissue removal. We propose that although these models hold for deformable metal surfaces, enamel works differently. Hydroxyapatite crystallites are "glued" together by proteins, and tissue removal requires only that contact pressure be sufficient to break the bonds holding enamel together.


Assuntos
Proteínas do Esmalte Dentário/fisiologia , Dieta , Alimentos/efeitos adversos , Dente Molar/ultraestrutura , Paleodontologia/métodos , Abrasão Dentária/patologia , Alumínio , Cobre , Esmalte Dentário/fisiologia , Esmalte Dentário/ultraestrutura , Fricção , Dureza , Humanos , Técnicas In Vitro , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Microesferas , Modelos Biológicos , Nanosferas/efeitos adversos , Tamanho da Partícula , Ligação Proteica , Dióxido de Silício , Espectrometria por Raios X , Propriedades de Superfície , Abrasão Dentária/etiologia , Zinco
6.
Nanotoxicology ; 9(2): 190-200, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24787691

RESUMO

A facile room-temperature method was used to prepare phosphatidylserine (PS)-poly(ethylene glycol) (PEG)/calcium phosphate (CaP) nanospheres (PS-poly(ethylene glycol) methyl ether/CaP nanospheres). Transmission electron microscopy (TEM) results confirmed that the PS-PEG/CaP porous nanospheres were spherical with a diameter of 8-12 nm. X-ray and thermo-gravimetric analysis (TGA) results also confirmed that the PS-PEG micelle was packed in the CaP shell. PS-PEG/CaP nanospheres exhibited little effect on the hemolysis, coagulation characteristics of blood and inflammatory response, demonstrating a negligible cytotoxicity response in LO2 liver cells. Experiments performed in zebrafish demonstrated that the PS-PEG/CaP nanospheres had a long circulatory residence time and did not induce apoptosis in zebrafish. Taken together, these results suggest that the PS-PEG/CaP nanospheres have great potential to be used as a drug carrier.


Assuntos
Fosfatos de Cálcio/efeitos adversos , Hepatócitos/fisiologia , Nanocápsulas/efeitos adversos , Nanocápsulas/química , Nanosferas/efeitos adversos , Peixe-Zebra/fisiologia , Animais , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/síntese química , Fosfatos de Cálcio/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Teste de Materiais , Taxa de Depuração Metabólica/fisiologia , Nanosferas/química , Tamanho da Partícula , Fosfatidilserinas/efeitos adversos , Fosfatidilserinas/química , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Coelhos , Taxa de Sobrevida , Distribuição Tecidual
7.
J Diabetes Sci Technol ; 6(4): 773-9, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22920801

RESUMO

Barriers to the use of prandial insulin regimens include inadequate synchronization of insulin action to postprandial plasma glucose excursions as well as a significant risk of hypoglycemia and weight gain. Technosphere® insulin (TI) is an inhaled ultra-rapid-acting human insulin that is quickly absorbed in the alveoli. With a time to maximum plasma drug concentration of approximately 14 min and a time to maximum effect of 35 to 40 min, TI more closely matches the postprandial insulin concentrations seen in nondiabetic individuals. Studies have shown that long-term administration of prandial TI in combination with long-acting basal insulin results in reductions in hemoglobin A1c comparable to conventional subcutaneously injected prandial insulins but with improved control of early postprandial BG. Furthermore, TI has been associated with less weight gain and a lower incidence of hypoglycemia, which may enhance patient satisfaction and acceptability of insulin therapy. This review discusses the clinical properties of TI and proposes strategies for optimal use.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Insulina de Ação Curta/administração & dosagem , Insulina de Ação Curta/farmacologia , Período Pós-Prandial/efeitos dos fármacos , Administração por Inalação , Diabetes Mellitus/sangue , Diabetes Mellitus/metabolismo , Sistemas de Liberação de Medicamentos/instrumentação , Ingestão de Alimentos/efeitos dos fármacos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Insulina de Ação Curta/efeitos adversos , Insulina de Ação Curta/farmacocinética , Nanosferas/administração & dosagem , Nanosferas/efeitos adversos , Satisfação do Paciente/estatística & dados numéricos
9.
ACS Nano ; 2(1): 85-96, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19206551

RESUMO

The exponential increase in the number of new nanomaterials that are being produced increases the likelihood of adverse biological effects in humans and the environment. In this study we compared the effects of cationic nanoparticles in five different cell lines that represent portal-of-entry or systemic cellular targets for engineered nanoparticles. Although 60 nm NH(2)-labeled polystyrene (PS) nanospheres were highly toxic in macrophage (RAW 264.7) and epithelial (BEAS-2B) cells, human microvascular endothelial (HMEC), hepatoma (HEPA-1), and pheochromocytoma (PC-12) cells were relatively resistant to particle injury. While the death pathway in RAW 264.7 cells involves caspase activation, the cytotoxic response in BEAS-2B cells is more necrotic in nature. Using fluorescent-labeled NH(2)-PS, we followed the routes of particle uptake. Confocal microscopy showed that the cationic particles entered a LAMP-1 positive lysosomal compartment in RAW 264.7 cells from where the particles could escape by lysosomal rupture. A proton pump inhibitor interfered in this pathway. Subsequent deposition of the particles in the cytosol induced an increase in mitochondrial Ca(2+) uptake and cell death that could be suppressed by cyclosporin A (CsA). In contrast, NH(2)-PS toxicity in BEAS-2B cells did not involve the LAMP-1 endosomal compartment, stimulation of proton pump activity, or an increase in mitochondrial Ca(2+). Particles were taken up by caveolae, and their toxicity could be disrupted by cholesterol extraction from the surface membrane. Although the particles induced mitochondrial damage and ATP depletion, CsA did not affect cytotoxicity. Cationic particles were taken up into HEPA-1, HMEC, and PC-12 cells, but this did not lead to lysosomal permeabilization, increased Ca(2+) flux, or mitochondrial damage. Taken together, the results of this study demonstrate the importance of cell-specific uptake mechanisms and pathways that could lead to sensitivity or resistance to cationic particle toxicity.


Assuntos
Endocitose , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Nanosferas/toxicidade , Poliestirenos/metabolismo , Poliestirenos/toxicidade , Aminas/química , Animais , Cálcio/metabolismo , Cavéolas/efeitos dos fármacos , Cavéolas/metabolismo , Linhagem Celular , Citotoxinas/antagonistas & inibidores , Citotoxinas/química , Citotoxinas/metabolismo , Citotoxinas/toxicidade , Corantes Fluorescentes/química , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espaço Intracelular/ultraestrutura , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Macrolídeos/farmacologia , Camundongos , Mitocôndrias/metabolismo , Nanosferas/efeitos adversos , Nanosferas/química , Especificidade de Órgãos , Permeabilidade/efeitos dos fármacos , Pneumonia/induzido quimicamente , Pneumonia/patologia , Poliestirenos/antagonistas & inibidores , Poliestirenos/química , beta-Ciclodextrinas/farmacologia
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