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1.
Food Chem Toxicol ; 181: 114109, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37858841

RESUMO

We investigated a possible toxic effect induced by chronic exposure to free curcumin and curcumin-loaded nanocapsules in Drosophila melanogaster, enabling safe applications. Flies of both sexes were divided into groups: control group; free curcumin at concentrations of 10, 30, 100, 300, 900, and 3000 µM; curcumin-loaded nanocapsules at concentrations of 10, 30, 100, and 300 µM. Initially, the diet consumption test was evaluated in flies exposed to different concentrations. During the 10-day treatment, the flies were evaluated for percentage survival. After the treatment, behaviors (geotaxis negative and open field), acetylcholinesterase activity (AChE), and oxidative stress parameters (reactive species (RS) and thiobarbituric acid reactive substances (TBARS) levels, Glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) enzymes activity, erythroid-derived nuclear factor 2 (Nrf2) immunoreactivity, and cellular metabolic capacity, were assessed. No significant difference in diet consumption, indicating that the flies equally consumed the different concentrations of free curcumin and the curcumin-loaded nanocapsules. Was observed that free curcumin and curcumin-loaded nanocapsules increased survival, locomotor and exploratory performance, decreased AChE activity, RS and TBARS levels, increased GST, SOD and CAT activity, Nrf2 and viable cells compared to the control. The chronic treatment did not cause toxicity, suggesting that nanoencapsulation of curcumin could be explored.


Assuntos
Curcumina , Nanocápsulas , Animais , Masculino , Feminino , Drosophila melanogaster , Curcumina/toxicidade , Nanocápsulas/toxicidade , Acetilcolinesterase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico , Estresse Oxidativo , Antioxidantes/farmacologia , Superóxido Dismutase/metabolismo , Catalase/metabolismo
2.
Drug Chem Toxicol ; 46(1): 155-165, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34930069

RESUMO

Curcumin is an active polyphenol substance found in the highest concentrations in the roots of Curcuma longa. Its health benefits have led to recent increases in the consumption of curcumin. It has anti-inflammatory and antioxidant activities and is a potent neuroprotective against diseases of the brain. Nevertheless, its low bioavailability and its relative difficulty crossing the blood-brain barrier limit curcumin's use for these purposes. Curcumin-loaded nanoparticles may be an effective treatment for several diseases although there is a paucity of studies reporting its safety in the central nervous system (CNS). Therefore, this study aimed to identify non-neurotoxic concentrations of free curcumin and two nanoformulations of curcumin. Cell lines BV-2 and SH-SY5Y, both originating from the CNS, were evaluated after 24, 48, and 72 h of treatment with free curcumin and nanocapsules We measured viability, proliferation, and dsDNA levels. We measured levels of reactive oxygen species and nitric oxide as proxies for oxidative stress in culture supernatants. We found that free curcumin was toxic at 10 and 20 µM, principally at 72 h. Nanoformulations were more neurotoxic than the free form. Safe concentrations of free curcumin are between 1-5 µM, and these concentrations were lower for nanoformulations. We determined the ideal concentrations of free curcumin and nanocapsules serving as a basis for studies of injuries that affect the CNS.


Assuntos
Curcumina , Nanocápsulas , Neuroblastoma , Humanos , Curcumina/farmacologia , Nanocápsulas/toxicidade , Linhagem Celular , Estresse Oxidativo
3.
Artigo em Inglês | MEDLINE | ID: mdl-36182082

RESUMO

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.


Assuntos
Quitosana , Nanocápsulas , Animais , Nanocápsulas/toxicidade , Nanocápsulas/química , Caenorhabditis elegans , Quitosana/toxicidade , Polissorbatos/toxicidade , Polímeros/química , Superóxido Dismutase
4.
J Hazard Mater ; 422: 126853, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34399229

RESUMO

Recently, size-controlled pesticide microcapsule (MC) delivery systems have played an important role in precision farming development; however, the potential environmental hazards of MCs with different particle sizes have not been fully characterized. In this study, we prepared a series of lambda-cyhalothrin (LC)-MCs with nano and micron-scale capsule sizes (average diameters of 209.4 nm, MC-N; 2.41 µm, MC-S; 4.87 µm, MC-M; and 12.41 µm, MC-L). The assessment results showed that the release and sedimentation behavior of LC-MCs in water and toxicity to zebrafish at three life stages were all particle size-dependent. As the diameter distribution of approximately 100 nm extended to the micron scale (~27 µm), the capsules released more slowly and sunk more quickly in water. In addition, micron-sized LC-MC exposure resulted in significantly less fish mortality and malformations of larvae and embryos compared with nanosized LC-MC exposure. The highest accumulation of MC-N in the gill and the severest toxicity to larvae suggested that the smaller size and stronger permeability of nanocapsules would pose unpredictable consequences for nontargeted organisms. The obvious toxicological differences of LC-MCs toward aquatic organisms implies that regulating MC production in an appropriate size range is an important prerequisite for achieving efficient but safe pesticide applications.


Assuntos
Nanocápsulas , Piretrinas , Poluentes Químicos da Água , Animais , Embrião não Mamífero , Larva , Nanocápsulas/toxicidade , Nitrilas , Piretrinas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
5.
Nanoscale ; 13(37): 15647-15658, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34532728

RESUMO

Nanocapsules are a promising controlled release formulation for foliar pest control. However, the complicated process and high cost limit widespread use in agriculture, so a simpler and more convenient preparation system is urgently needed. Meanwhile, under complex field conditions, the advantageous mechanism of the nanosize effect and sustained release have no quantitative and detailed study. In this study, a reactive emulsifier (OP-10) is used to participate in the interfacial polymerization of the nanoemulsion, and polymer nanocapsules loaded with lambda-cyhalothrin (NCS@LC) are quickly and easily prepared to study the efficacy and synergistic mechanism of foliar pest control. As a result, the nanocapsule is about 150 nm with a stable core-shell structure. The nanoscale state increases the distribution and adhesion of the particles on the leaf surface, which increases the contact efficiency of pesticides under the different physiological stages and behavioral activities of the target organism. The shell structure provides sustained release characteristics and increases the UV resistance by about 2.5 times for pesticides. Compared with microcapsules loaded with lambda-cyhalothrin (CS@LC), NCS@LC not only shows rapid and synergistic insecticidal efficacy but also provides sustained insecticidal efficacy. The mortality of NCS is 3.4 times that of the nanosized emulsion in water (NEW) at the lowest concentration (0.5 mg L-1), and the control efficacy remained 77.3% after 7 days. Compared with NEW, NCS@LC provides excellent field efficacy, while LC50 for zebrafish is only 0.68 times without increasing the aquatic toxicity risk.


Assuntos
Inseticidas , Nanocápsulas , Piretrinas , Animais , Nanocápsulas/toxicidade , Nitrilas , Peixe-Zebra
6.
ACS Appl Mater Interfaces ; 13(30): 35494-35505, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34288640

RESUMO

Polymer nanocapsules, with a hollow structure, are increasingly finding widespread use as drug delivery carriers; however, quantitatively evaluating the bio-nano interactions of nanocapsules remains challenging. Herein, poly(ethylene glycol) (PEG)-based metal-phenolic network (MPN) nanocapsules of three sizes (50, 100, and 150 nm) are engineered via supramolecular template-assisted assembly and the effect of the nanocapsule size on bio-nano interactions is investigated using in vitro cell experiments, ex vivo whole blood assays, and in vivo rat models. To track the nanocapsules by mass cytometry, a preformed gold nanoparticle (14 nm) is encapsulated into each PEG-MPN nanocapsule. The results reveal that decreasing the size of the PEG-MPN nanocapsules from 150 to 50 nm leads to reduced association (up to 70%) with phagocytic blood cells in human blood and prolongs in vivo systemic exposure in rat models. The findings provide insights into MPN-based nanocapsules and represent a platform for studying bio-nano interactions.


Assuntos
Sangue/metabolismo , Estruturas Metalorgânicas/química , Nanocápsulas/química , Polietilenoglicóis/química , Pirogalol/análogos & derivados , Animais , Citometria de Fluxo/métodos , Ouro/química , Ouro/metabolismo , Ouro/farmacocinética , Ouro/toxicidade , Humanos , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Estruturas Metalorgânicas/metabolismo , Estruturas Metalorgânicas/farmacocinética , Estruturas Metalorgânicas/toxicidade , Camundongos , Nanocápsulas/toxicidade , Tamanho da Partícula , Polietilenoglicóis/metabolismo , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/toxicidade , Pirogalol/metabolismo , Pirogalol/farmacocinética , Pirogalol/toxicidade , Células RAW 264.7 , Ratos Sprague-Dawley
7.
Carbohydr Polym ; 267: 118152, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119127

RESUMO

Herein, we demonstrate a novel UV-induced decomposable nanocapsule of natural polysaccharide (HA-azo/PDADMAC). The nanocapsules are fabricated based on layer-by-layer co-assembly of anionic azobenzene functionalized hyaluronic acid (HA-azo) and cationic poly diallyl dimethylammonium chloride (PDADMAC). When the nanocapsules are exposed to 365 nm light, ultraviolet photons can trigger the photo-isomerization of azobenzene groups in the framework. The nanocapsules could decompose from large-sized nanocapsules to small fragments. Due to their optimized original size (~180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation and achieve high tumor accumulation. It can fast eliminate nanocapsules from tumor and release the loaded drugs for chemotherapy after UV-induced dissociation. Besides, HA is an endogenous polysaccharide that shows intrinsic targetability to CD44 receptors on surface of cancer cells. The intracellular experiment shows that the HA-azo/PDADMAC nanocapsules with CD44 targeting ability and UV-controlled intracellular drug release are promising for cancer chemotherapy.


Assuntos
Compostos Azo/química , Portadores de Fármacos/química , Ácido Hialurônico/química , Nanocápsulas/química , Antineoplásicos/química , Compostos Azo/metabolismo , Compostos Azo/efeitos da radiação , Compostos Azo/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/efeitos da radiação , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos/efeitos da radiação , Endocitose/fisiologia , Células Hep G2 , Humanos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/síntese química , Ácido Hialurônico/metabolismo , Ácido Hialurônico/toxicidade , Nanocápsulas/efeitos da radiação , Nanocápsulas/toxicidade , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Polietilenos/química , Polietilenos/toxicidade , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/toxicidade , Dióxido de Silício/síntese química , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Estereoisomerismo , Raios Ultravioleta
8.
Carbohydr Polym ; 266: 118174, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34044962

RESUMO

In this study, a biocompatible folate-decorated reductive-responsive carboxymethylcellulose-based nanocapsules (FA-RCNCs) were designed and prepared via sonochemical method for targeted delivery and controlled release of hydrophobic drugs. The shell of FA-RCNCs was cross-linked by disulfide bonds formed from hydrosulfuryl groups on the thiolated carboxymethylcellulose (TCMC) and encapsulated hydrophobic drug dispersed in the oil phase into nanocapsules. Moreover, the size and morphology of drug loaded FA-RCNCs were characterized by DLS, SEM and CLSM which indicated that the synthesized nanocapsules have suitable size range and excellent stability for circulating in the bloodstream. The drug release rate of FA-RCNCs could be controlled by adjusting their sizes and shell thickness, which could be dominated by the concentration of TCMC and sonochemical conditions. Furthermore, the obtained FA-RCNCs could be ingested into Hela cells via folate-receptor (FR)-mediated endocytosis and quickly release drugs under reductive environment, which demonstrated that FA-RCNCs could become potential hydrophobic drugs carries for cancer therapy.


Assuntos
Carboximetilcelulose Sódica/química , Portadores de Fármacos/química , Ácido Fólico/análogos & derivados , Nanocápsulas/química , Carboximetilcelulose Sódica/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Ácido Fólico/toxicidade , Humanos , Nanocápsulas/toxicidade , Tiazóis/química , Ondas Ultrassônicas
10.
PLoS One ; 15(9): e0238823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970684

RESUMO

Mucoadhesive polymeric nanocapsules have attracted interest of researchers from different fields from natural sciences because of their ability to interact with the mucosa and increase drug permeation. Anesthesia by immersion causes absorption through the skin and gills of fish, so it is important to evaluate the exposure of these organs to drug nanosystems. Benzocaine (BENZ) is one of the most popular anesthetic agents used in fish anesthesia, but it has drawbacks because of its low bioavailability, resulting in weak absorption after immersion. Here we describe method developed for preparing and characterizing chitosan-coated PLGA mucoadhesive nanoparticles containing BENZ (NPMAs) for zebrafish immersion anesthesia. We determined the lowest effective concentration, characterized the interaction of the mucoadhesive system with fish, measured the anesthetic efficacy, and evaluated possible toxic effects in embryos and adults exposed to the nanoformulations. This study opens perspectives for using nanoformulations prepared with BENZ in aquaculture, allowing reduction of dosage as well as promoting more effective anesthesia and improved interaction with the mucoadhesive system of fish.


Assuntos
Anestesia/veterinária , Benzocaína/administração & dosagem , Nanocápsulas/administração & dosagem , Peixe-Zebra , Animais , Aquicultura , Quitosana/administração & dosagem , Quitosana/toxicidade , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Brânquias/efeitos dos fármacos , Nanocápsulas/toxicidade , Pele/efeitos dos fármacos
11.
Rev Bras Parasitol Vet ; 29(1): e013119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049139

RESUMO

The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.


Assuntos
Anti-Helmínticos/administração & dosagem , Trato Gastrointestinal/parasitologia , Monoterpenos/administração & dosagem , Nanocápsulas/administração & dosagem , Nematoides/efeitos dos fármacos , Infecções por Nematoides/tratamento farmacológico , Doenças dos Ovinos/tratamento farmacológico , Animais , Anti-Helmínticos/toxicidade , Fezes/parasitologia , Feminino , Camundongos , Monoterpenos/toxicidade , Nanocápsulas/toxicidade , Nematoides/classificação , Nematoides/isolamento & purificação , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas , Testes de Sensibilidade Parasitária , Reação em Cadeia da Polimerase em Tempo Real , Roedores , Ovinos , Doenças dos Ovinos/parasitologia , Testes de Toxicidade
12.
Sci Rep ; 10(1): 2110, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034197

RESUMO

Nanoencapsulation is a rapidly expanding technology to enclose cargo into inert material at the nanoscale size, which protects cargo from degradation, improves bioavailability and allows for controlled release. Encapsulation of drugs into functional nanocarriers enhances their specificity, targeting ability, efficiency, and effectiveness. Functionality may come from cell targeting biomolecules that direct nanocarriers to a specific cell or tissue. Delivery is usually mediated by diffusion and erosion mechanisms, but in some cases, this is not sufficient to reach the expected therapeutic effects. This work reports on the development of a new photoresponsive polymeric nanocarrier (PNc)-based nanobioconjugate (NBc) for specific photo-delivery of cargo into target cells. We readily synthesized the PNcs by modification of chitosan with ultraviolet (UV)-photosensitive azobenzene molecules, with Nile red and dofetilide as cargo models to prove the encapsulation/release concept. The PNcs were further functionalized with the cardiac targeting transmembrane peptide and efficiently internalized into cardiomyocytes, as a cell line model. Intracellular cargo-release was dramatically accelerated upon a very short UV-light irradiation time. Delivering cargo in a time-space controlled fashion by means of NBcs is a promising strategy to increase the intracellular cargo concentration, to decrease dose and cargo side effects, thereby improving the effectiveness of a therapeutic regime.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanocápsulas , Células A549/efeitos dos fármacos , Células A549/metabolismo , Linhagem Celular , Células Hep G2/efeitos dos fármacos , Células Hep G2/metabolismo , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Nanocápsulas/química , Nanocápsulas/efeitos da radiação , Nanocápsulas/toxicidade , Nanopartículas/química , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Raios Ultravioleta
13.
J Nanobiotechnology ; 18(1): 5, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907052

RESUMO

BACKGROUND: Lipid nanocapsules (LNCs) are promising vehicles for drug delivery. However, since not much was known about cellular toxicity of these nanoparticles in themselves, we have here investigated the mechanisms involved in LNC-induced intoxication of the three breast cancer cell lines MCF-7, MDA-MD-231 and MDA-MB-468. The LNCs used were made of Labrafac™ Lipophile WL1349, Lipoid® S75 and Solutol® HS15. RESULTS: High resolution SIM microscopy showed that the DiD-labeled LNCs ended up in lysosomes close to the membrane. Empty LNCs, i.e. without encapsulated drug, induced not only increased lysosomal pH, but also acidification of the cytosol and a rapid inhibition of protein synthesis. The cytotoxicity of the LNCs were measured for up to 72 h of incubation using the MTT assay and ATP measurements in all three cell lines, and revealed that MDA-MB-468 was the most sensitive cell line and MCF-7 the least sensitive cell line to these LNCs. The LNCs induced generation of reactive free oxygen species and lipid peroxidation. Experiments with knock-down of kinases in the near-haploid cell line HAP1 indicated that the kinase HRI is essential for the observed phosphorylation of eIF2α. Nrf2 and ATF4 seem to play a protective role against the LNCs in MDA-MB-231 cells, as knock-down of these factors sensitizes the cells to the LNCs. This is in contrast to MCF-7 cells where the knock-down of these factors had a minor effect on the toxicity of the LNCs. Inhibitors of ferroptosis provided a large protection against LNC toxicity in MDA-MB-231 cells, but not in MCF-7 cells. CONCLUSIONS: High doses of LNCs showed a different degree of toxicity on the three cell lines studied, i.e. MCF-7, MDA-MD-231 and MDA-MB-468 and affected signaling factors and the cell fate differently in these cell lines.


Assuntos
Lipídeos/toxicidade , Nanocápsulas/toxicidade , Fator 4 Ativador da Transcrição/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Endocitose/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Nanocápsulas/ultraestrutura , Oxirredução , Biossíntese de Proteínas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/efeitos dos fármacos
14.
J Nanosci Nanotechnol ; 20(3): 1486-1494, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492311

RESUMO

Galleria mellonella larvae is an invertebrate that has been extensively used as experimental model in the investigation of microbial virulence and efficacy of antimicrobial agents and can be used to provide faster and cheaper data than traditional test systems. Our objective was to propose the use of G. mellonella larvae as an In Vivo model to evaluate the toxicity of lipid-core nanocapsule (LNC) formulations having different surface coatings. Blank LNC formulations were coated with polysorbate 80 (LNC-1), lecithin and polysorbate 80 (LNC-2), and lecithin, chitosan and polysorbate 80 (LNC-3). Subsequently, the formulations were systemically administered to G. mellonella larvae at doses of 3.75×10-14, 3.75×10-13, 3.75×10-12, 3.75×10-11 and 3.75×10-10 mols of LNC per kg of larvae. The results demonstrated that those nanocapsules having neutral (LNC-1), negative (LNC-2) or positive (LNC-3) surface did not show acute toxicity effects in G. mellonella larvae. G. mellonella larvae is a viable and promising alternative for In Vivo nanotoxicological studies. We conclude that G. mellonella larvae can be used as an alternative model for the screening of the toxicity of polymeric nanocapsules functionalized with (i) polysorbate 80, (ii) lecithin and polysorbate 80, and (iii) lecithin, chitosan and polysorbate 80. Future studies can be now developed in order to evaluate their toxicity when loaded or functionalized with drugs.


Assuntos
Quitosana , Nanocápsulas , Animais , Quitosana/toxicidade , Composição de Medicamentos , Larva , Lipídeos , Nanocápsulas/toxicidade
15.
Biomacromolecules ; 21(2): 418-434, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31738540

RESUMO

Minimization of drug side effects is a hallmark of advanced targeted therapy. Herein we describe the synthesis of polysaccharide-based nanocapsules prepared from furcellaran and chitosan via layer-by-layer deposition using electrostatic interaction. Using doxorubicin as a model drug, prepared nanocapsules showed excellent drug loading properties and release influence by pH and stability. Targeted delivery of doxorubicin was achieved by nanocapsule surface modification using homing peptide (seq SMSIARLC). The synthesized nanocapsules possess excellent compatibility to eukaryotic organisms. In the case of nonmalignant cells (PNT1A and HEK-293), toxicity tests revealed the absences of DNA fragmentation, apoptosis, necrosis, and also disruption of erythrocyte membranes. In contrast, results from treatment of malignant cell lines (MDA-MB-231 and PC3) indicate good anticancer effects of synthesized bionanomaterial. Internalization studies revealed the nanocapsule's ability to enter the malignant cell lines by endocytosis and triggering the apoptosis. The occurrence of apoptosis is mostly connected to the presence of ROS and inability of DNA damage reparation. Additionally, the obtained results strongly indicate that peptide modification increases the speed of nanocapsule internalization into malignant cell lines while simultaneously nonmalignant cell lines are untouched by nanocapsules highlighting the strong selectivity of the peptide.


Assuntos
Preparações de Ação Retardada , Doxorrubicina/farmacocinética , Nanocápsulas/química , Alginatos/química , Linhagem Celular Tumoral , Quitosana/química , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Pessoa de Meia-Idade , Nanocápsulas/administração & dosagem , Nanocápsulas/toxicidade , Peptídeos/química , Peptídeos/metabolismo , Gomas Vegetais/química , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Polieletrólitos/química , Testes de Toxicidade
16.
Rev. bras. parasitol. vet ; 29(1): e013119, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1058018

RESUMO

Abstract The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.


Resumo O objetivo deste trabalho foi avaliar a eficácia do acetato de carvacrila (ACV) e do ACV nanoencapsulado (nACV) sobre nematóides gastrintestinais de ovinos. O ACV foi nanoencapsulado com quitosana/goma arábica e foi analisada a eficácia de nanoencapsulamento (EE), o rendimento, potencial zeta, morfologia das nanopartículas e cinética de liberação em pH 3 e 8. Foram avaliadas as toxicidades aguda e subcrônica em roedores e a redução da contagem de ovos nas fezes (RCOF) de ovinos. Os ovinos foram divididos em quatro grupos (n = 10): G1, 250 mg/kg ACV; G2, 250 mg/kg de nACV; G3, matriz polimérica e G4: 2,5 mg/kg de monepantel. A EE e o rendimento de nACV foram de 65% e 57%, respectivamente. A morfologia das nanopartículas foi esférica, tamanho (810,6±286,7 nm), potencial zeta no pH 3,2 (+18,3 mV) e a liberação de 50% de CVA nos pHs 3 e 8 ocorreu às 200 e 10 h, respectivamente. nACV apresentou DL50 de 2.609 mg/kg. ACV, nACV e o monepantel reduziram a contagem de ovos por grama de fezes (opg) em 57,7%, 51,1% e 97,7%, respectivamente. A contagem de opg de ovelhas tratadas com ACV e nCVA não diferiu do controle negativo (P>0,05). O nanoencapsulamento reduziu a toxicidade do AVC; no entanto, nACV e ACV apresentaram resultados semelhantes na RCOF.


Assuntos
Animais , Feminino , Camundongos , Ratos , Doenças dos Ovinos/parasitologia , Monoterpenos/farmacologia , Trato Gastrointestinal/parasitologia , Nanocápsulas/administração & dosagem , Anti-Helmínticos/farmacologia , Infecções por Nematoides/veterinária , Contagem de Ovos de Parasitas , Doenças dos Ovinos/tratamento farmacológico , Benzimidazóis/farmacologia , Resistência a Medicamentos/efeitos dos fármacos , Ovinos/parasitologia , Levamisol/farmacologia , Ratos Wistar/sangue , Testes de Toxicidade , Testes de Sensibilidade Parasitária , Monoterpenos/toxicidade , Monoterpenos/uso terapêutico , Nanocápsulas/toxicidade , Nanocápsulas/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Hemoncose/tratamento farmacológico , Haemonchus/isolamento & purificação , Haemonchus/efeitos dos fármacos , Helmintíase Animal/tratamento farmacológico , Anti-Helmínticos/toxicidade , Anti-Helmínticos/uso terapêutico , Camundongos , Infecções por Nematoides/tratamento farmacológico
17.
Int J Nanomedicine ; 14: 9587-9602, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824153

RESUMO

BACKGROUND: The functionalization of a nanoparticle surface with PEG (polyethylene glycol) is an approach most often used for extending nanomaterial circulation time, enhancing its delivery and retention in the target tissues, and decreasing systemic toxicity of nanocarriers and their cargos. However, because PEGylated nanomedicines were reported to induce immune response including production of anti-PEG antibodies, activation of the complement system as well as hypersensitivity reactions, hydrophilic polymers other than PEG are gaining interest as its replacement in nanomaterial functionalization. Here, we present the results of in vivo evaluation of polyelectrolyte nanocapsules with biodegradable, polyelectrolyte multilayer shells consisting of poly-l-lysine (PLL) and poly-l-glutamic (PGA) acid as a potential drug delivery system. We compared the effects of nanocapsules functionalized with two different "stealth" polymers as the external layer of tested nanocapsules was composed of PGA (PGA-terminated nanocapsules, NC-PGA) or the copolymer of poly-l-lysine and polyethylene glycol (PEG-terminated nanocapsules, NC-PEG). METHODS: Nanocapsules pharmacokinetics, biodistribution and routes of eliminations were analysed postmortem by fluorescence intensity measurement. Toxicity of intravenously injected nanocapsules was evaluated with analyses of blood morphology and biochemistry and by histological tissue analysis. DNA integrity was determined by comet assay, cytokine profiling was performed using flow cytometer and detection of antibodies specific to PEG was performed by ELISA assay. RESULTS: We found that NC-PGA and NC-PEG had similar pharmacokinetic and biodistribution profiles and both were eliminated by hepatobiliary and renal clearance. Biochemical and histopathological evaluation of long-term toxicity performed after a single as well as repeated intravenous injections of nanomaterials demonstrated that neither NC-PGA nor NC-PEG had any acute or chronic hemato-, hepato- or nephrotoxic effects. In contrast to NC-PGA, repeated administration of NC-PEG resulted in prolonged increased serum levels of a number of cytokines. CONCLUSION: Our results indicate that NC-PEG may cause undesirable activation of the immune system. Therefore, PGA compares favorably with PEG in equipping nanomaterials with stealth properties. Our research points to the importance of a thorough assessment of the potential influence of nanomaterials on the immune system.


Assuntos
Nanocápsulas/toxicidade , Polieletrólitos/farmacocinética , Polieletrólitos/toxicidade , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/toxicidade , Ácido Poliglutâmico/farmacocinética , Ácido Poliglutâmico/toxicidade , Animais , Citocinas/sangue , Sistemas de Liberação de Medicamentos , Feminino , Fluorescência , Camundongos Endogâmicos BALB C , Nanocápsulas/química , Especificidade de Órgãos/efeitos dos fármacos , Polieletrólitos/química , Polietilenoglicóis/química , Ácido Poliglutâmico/química , Rodaminas/química , Distribuição Tecidual , Regulação para Cima/efeitos dos fármacos
18.
Chem Commun (Camb) ; 55(92): 13820-13823, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31664274

RESUMO

A supramolecular nanocapsule was constructed by the ternary host-guest complexation of azobenzene (Azo) and methylviologen (MV) to cucurbit[8]uril (CB[8]) and the subsequent self-assembly. The supramolecular nanocapsule with both glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities can mimic the intracellular enzymatic reactive oxygen species (ROS) defense system.


Assuntos
Antioxidantes/química , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Nanocápsulas/química , Células 3T3 , Animais , Compostos Azo/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Glutationa Peroxidase/química , Glutationa Peroxidase/metabolismo , Camundongos , Microscopia Confocal , Nanocápsulas/toxicidade , Paraquat/química , Espécies Reativas de Oxigênio/química , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo
19.
J Mater Chem B ; 7(42): 6592-6603, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31589221

RESUMO

Management of infected wounds is one of the most costly procedures in the health care sector. Burn wounds are of significant importance due to the high infection risk that can possibly lead to severe consequences such as sepsis. Because antibiotic wound treatments have caused increasing antibiotic resistance in bacteria, there is currently a strong need for alternative strategies. Therefore, we developed new antimicrobial wound dressings consisting of pH-responsive human serum albumin/silk fibroin nanocapsules immobilized onto cotton/polyethylene terephthalate (PET) blends loaded with eugenol, which is an antimicrobial phenylpropanoid. Ultrasound-assisted production of eugenol-loaded nanocapsules resulted in particle sizes (hydrodynamic radii) between 319.73 ± 17.50 and 574.00 ± 92.76 nm and zeta potentials ranging from -10.39 ± 1.99 mV to -12.11 ± 0.59 mV. Because recent discoveries have indicated that the sweat glands contribute to wound reepithelialisation, release studies of eugenol were conducted in different artificial sweat formulas that varied in pH. Formulations containing 10% silk fibroin with lower degradation degree exhibited the highest release of 41% at pH 6.0. After immobilization, the functionalized cotton/PET blends were able to inhibit 81% of Staphylococcus aureus and 33% of Escherichia coli growth. Particle uniformity, silk fibroin concentration, and high surface-area-to-volume ratio of the produced nanocapsules were identified as the contributing factors leading to high antimicrobial activities against both strains. Therefore, the production of antimicrobial textiles using nanocapsules loaded with an active natural compound that will not contribute to antibiotic resistance is seen as a potential future alternative to commercially available antiseptic wound dressings.


Assuntos
Antibacterianos/farmacologia , Fibra de Algodão , Eugenol/farmacologia , Nanocápsulas/química , Polietilenotereftalatos/química , Materiais Inteligentes/farmacologia , Antibacterianos/química , Antibacterianos/toxicidade , Bandagens , Hidrolases de Éster Carboxílico/química , Linhagem Celular , Celulase/química , Fibra de Algodão/toxicidade , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Eugenol/química , Eugenol/toxicidade , Fibroínas/química , Fibroínas/toxicidade , Humanos , Nanocápsulas/toxicidade , Polietilenotereftalatos/toxicidade , Albumina Sérica Humana/química , Albumina Sérica Humana/toxicidade , Materiais Inteligentes/química , Materiais Inteligentes/toxicidade , Staphylococcus aureus/efeitos dos fármacos
20.
Chem Commun (Camb) ; 55(60): 8876-8879, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31286121

RESUMO

Here we report template-free synthesis of imine-linked calix[4]arene hollow nanocapsules and their utility in the effective delivery of a poorly soluble cancer drug into tumor cells. These stimuli-responsive nanocapsules show high drug loading and release which resulted in a 40-fold higher cytotoxicity for breast cancer cell line over normal cells.


Assuntos
Antineoplásicos/farmacologia , Calixarenos/química , Camptotecina/farmacologia , Portadores de Fármacos/química , Nanocápsulas/química , Fenóis/química , Antineoplásicos/química , Calixarenos/síntese química , Calixarenos/toxicidade , Camptotecina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Nanocápsulas/toxicidade , Fenóis/síntese química , Fenóis/toxicidade
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