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1.
Food Chem Toxicol ; 181: 114109, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37858841

RÉSUMÉ

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.


Sujet(s)
Curcumine , Nanocapsules , Animaux , Mâle , Femelle , Drosophila melanogaster , Curcumine/toxicité , Nanocapsules/toxicité , Acetylcholinesterase/métabolisme , Facteur-2 apparenté à NF-E2/métabolisme , Substances réactives à l'acide thiobarbiturique , Stress oxydatif , Antioxydants/pharmacologie , Superoxide dismutase/métabolisme , Catalase/métabolisme
2.
Drug Chem Toxicol ; 46(1): 155-165, 2023 Jan.
Article de Anglais | MEDLINE | ID: mdl-34930069

RÉSUMÉ

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.


Sujet(s)
Curcumine , Nanocapsules , Neuroblastome , Humains , Curcumine/pharmacologie , Nanocapsules/toxicité , Lignée cellulaire , Stress oxydatif
3.
Article de Anglais | MEDLINE | ID: mdl-36182082

RÉSUMÉ

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.


Sujet(s)
Chitosane , Nanocapsules , Animaux , Nanocapsules/toxicité , Nanocapsules/composition chimique , Caenorhabditis elegans , Chitosane/toxicité , Polysorbates/toxicité , Polymères/composition chimique , Superoxide dismutase
4.
J Hazard Mater ; 422: 126853, 2022 01 15.
Article de Anglais | MEDLINE | ID: mdl-34399229

RÉSUMÉ

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.


Sujet(s)
Nanocapsules , Pyréthrines , Polluants chimiques de l'eau , Animaux , Embryon non mammalien , Larve , Nanocapsules/toxicité , Nitriles , Pyréthrines/toxicité , Polluants chimiques de l'eau/toxicité , Danio zébré
5.
Nanoscale ; 13(37): 15647-15658, 2021 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-34532728

RÉSUMÉ

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.


Sujet(s)
Insecticides , Nanocapsules , Pyréthrines , Animaux , Nanocapsules/toxicité , Nitriles , Danio zébré
6.
ACS Appl Mater Interfaces ; 13(30): 35494-35505, 2021 Aug 04.
Article de Anglais | MEDLINE | ID: mdl-34288640

RÉSUMÉ

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.


Sujet(s)
Sang/métabolisme , Réseaux organométalliques/composition chimique , Nanocapsules/composition chimique , Polyéthylène glycols/composition chimique , Pyrogallol/analogues et dérivés , Animaux , Cytométrie en flux/méthodes , Or/composition chimique , Or/métabolisme , Or/pharmacocinétique , Or/toxicité , Humains , Mâle , Nanoparticules métalliques/composition chimique , Nanoparticules métalliques/toxicité , Réseaux organométalliques/métabolisme , Réseaux organométalliques/pharmacocinétique , Réseaux organométalliques/toxicité , Souris , Nanocapsules/toxicité , Taille de particule , Polyéthylène glycols/métabolisme , Polyéthylène glycols/pharmacocinétique , Polyéthylène glycols/toxicité , Pyrogallol/métabolisme , Pyrogallol/pharmacocinétique , Pyrogallol/toxicité , Cellules RAW 264.7 , Rat Sprague-Dawley
7.
Carbohydr Polym ; 267: 118152, 2021 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-34119127

RÉSUMÉ

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.


Sujet(s)
Composés azoïques/composition chimique , Vecteurs de médicaments/composition chimique , Acide hyaluronique/composition chimique , Nanocapsules/composition chimique , Antinéoplasiques/composition chimique , Composés azoïques/métabolisme , Composés azoïques/effets des radiations , Composés azoïques/toxicité , Survie cellulaire/effets des médicaments et des substances chimiques , Doxorubicine/composition chimique , Vecteurs de médicaments/métabolisme , Vecteurs de médicaments/effets des radiations , Vecteurs de médicaments/toxicité , Libération de médicament/effets des radiations , Endocytose/physiologie , Cellules HepG2 , Humains , Antigènes CD44/métabolisme , Acide hyaluronique/synthèse chimique , Acide hyaluronique/métabolisme , Acide hyaluronique/toxicité , Nanocapsules/effets des radiations , Nanocapsules/toxicité , Nanoparticules/composition chimique , Nanoparticules/métabolisme , Nanoparticules/toxicité , Polyéthylènes/composition chimique , Polyéthylènes/toxicité , Composés d'ammonium quaternaire/composition chimique , Composés d'ammonium quaternaire/toxicité , Silice/synthèse chimique , Silice/composition chimique , Silice/toxicité , Stéréoisomérie , Rayons ultraviolets
8.
Carbohydr Polym ; 266: 118174, 2021 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-34044962

RÉSUMÉ

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.


Sujet(s)
Carboxyméthylcellulose de sodium/composition chimique , Vecteurs de médicaments/composition chimique , Acide folique/analogues et dérivés , Nanocapsules/composition chimique , Carboxyméthylcellulose de sodium/toxicité , Lignée cellulaire tumorale , Survie cellulaire/effets des médicaments et des substances chimiques , Coumarines/composition chimique , Vecteurs de médicaments/synthèse chimique , Vecteurs de médicaments/toxicité , Libération de médicament , Acide folique/toxicité , Humains , Nanocapsules/toxicité , Thiazoles/composition chimique , Ondes ultrasonores
10.
PLoS One ; 15(9): e0238823, 2020.
Article de Anglais | MEDLINE | ID: mdl-32970684

RÉSUMÉ

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.


Sujet(s)
Anesthésie/médecine vétérinaire , Benzocaïne/administration et posologie , Nanocapsules/administration et posologie , Danio zébré , Animaux , Aquaculture , Chitosane/administration et posologie , Chitosane/toxicité , Vecteurs de médicaments/administration et posologie , Vecteurs de médicaments/toxicité , Libération de médicament , Branchies/effets des médicaments et des substances chimiques , Nanocapsules/toxicité , Peau/effets des médicaments et des substances chimiques
11.
Sci Rep ; 10(1): 2110, 2020 02 07.
Article de Anglais | MEDLINE | ID: mdl-32034197

RÉSUMÉ

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.


Sujet(s)
Systèmes de délivrance de médicaments/méthodes , Nanocapsules , Cellules A549/effets des médicaments et des substances chimiques , Cellules A549/métabolisme , Lignée cellulaire , Cellules HepG2/effets des médicaments et des substances chimiques , Cellules HepG2/métabolisme , Humains , Myocytes cardiaques/effets des médicaments et des substances chimiques , Myocytes cardiaques/métabolisme , Nanocapsules/composition chimique , Nanocapsules/effets des radiations , Nanocapsules/toxicité , Nanoparticules/composition chimique , Nanoparticules/effets des radiations , Nanoparticules/toxicité , Rayons ultraviolets
12.
Rev Bras Parasitol Vet ; 29(1): e013119, 2020.
Article de Anglais | MEDLINE | ID: mdl-32049139

RÉSUMÉ

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.


Sujet(s)
Anthelminthiques/administration et posologie , Tube digestif/parasitologie , Monoterpènes/administration et posologie , Nanocapsules/administration et posologie , Nematoda/effets des médicaments et des substances chimiques , Nématodoses/traitement médicamenteux , Maladies des ovins/traitement médicamenteux , Animaux , Anthelminthiques/toxicité , Fèces/parasitologie , Femelle , Souris , Monoterpènes/toxicité , Nanocapsules/toxicité , Nematoda/classification , Nematoda/isolement et purification , Nématodoses/parasitologie , Numération des oeufs de parasites , Tests de sensibilité parasitaire , Réaction de polymérisation en chaine en temps réel , Rodentia , Ovis , Maladies des ovins/parasitologie , Tests de toxicité
13.
J Nanobiotechnology ; 18(1): 5, 2020 Jan 06.
Article de Anglais | MEDLINE | ID: mdl-31907052

RÉSUMÉ

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.


Sujet(s)
Lipides/toxicité , Nanocapsules/toxicité , Facteur de transcription ATF-4/métabolisme , Mort cellulaire/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale , Endocytose/effets des médicaments et des substances chimiques , Ferroptose/effets des médicaments et des substances chimiques , Homéostasie/effets des médicaments et des substances chimiques , Humains , Concentration en ions d'hydrogène , Lysosomes/effets des médicaments et des substances chimiques , Lysosomes/métabolisme , Facteur-2 apparenté à NF-E2/métabolisme , Nanocapsules/ultrastructure , Oxydoréduction , Biosynthèse des protéines/effets des médicaments et des substances chimiques , Espèces réactives de l'oxygène/métabolisme , Stress physiologique/effets des médicaments et des substances chimiques
14.
J Nanosci Nanotechnol ; 20(3): 1486-1494, 2020 03 01.
Article de Anglais | MEDLINE | ID: mdl-31492311

RÉSUMÉ

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.


Sujet(s)
Chitosane , Nanocapsules , Animaux , Chitosane/toxicité , Préparation de médicament , Larve , Lipides , Nanocapsules/toxicité
15.
Biomacromolecules ; 21(2): 418-434, 2020 02 10.
Article de Anglais | MEDLINE | ID: mdl-31738540

RÉSUMÉ

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.


Sujet(s)
Préparations à action retardée , Doxorubicine/pharmacocinétique , Nanocapsules/composition chimique , Alginates/composition chimique , Lignée cellulaire tumorale , Chitosane/composition chimique , Doxorubicine/administration et posologie , Systèmes de délivrance de médicaments/méthodes , Libération de médicament , Femelle , Cellules HEK293 , Hémolyse/effets des médicaments et des substances chimiques , Humains , Concentration en ions d'hydrogène , Adulte d'âge moyen , Nanocapsules/administration et posologie , Nanocapsules/toxicité , Peptides/composition chimique , Peptides/métabolisme , Gommes végétales/composition chimique , Antigènes CD31/métabolisme , Polyélectrolytes/composition chimique , Tests de toxicité
16.
Rev. bras. parasitol. vet ; 29(1): e013119, 2020. tab, graf
Article de Anglais | LILACS | ID: biblio-1058018

RÉSUMÉ

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.


Sujet(s)
Animaux , Femelle , Souris , Rats , Maladies des ovins/parasitologie , Monoterpènes/pharmacologie , Tube digestif/parasitologie , Nanocapsules/administration et posologie , Anthelminthiques/pharmacologie , Nématodoses/médecine vétérinaire , Numération des oeufs de parasites , Maladies des ovins/traitement médicamenteux , Benzimidazoles/pharmacologie , Résistance aux substances/effets des médicaments et des substances chimiques , Ovis/parasitologie , Lévamisole/pharmacologie , Rat Wistar/sang , Tests de toxicité , Tests de sensibilité parasitaire , Monoterpènes/toxicité , Monoterpènes/usage thérapeutique , Nanocapsules/toxicité , Nanocapsules/usage thérapeutique , Réaction de polymérisation en chaine en temps réel , Infections à Haemonchus/traitement médicamenteux , Haemonchus/isolement et purification , Haemonchus/effets des médicaments et des substances chimiques , Helminthoses animales/traitement médicamenteux , Anthelminthiques/toxicité , Anthelminthiques/usage thérapeutique , Souris , Nématodoses/traitement médicamenteux
17.
Int J Nanomedicine ; 14: 9587-9602, 2019.
Article de Anglais | MEDLINE | ID: mdl-31824153

RÉSUMÉ

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.


Sujet(s)
Nanocapsules/toxicité , Polyélectrolytes/pharmacocinétique , Polyélectrolytes/toxicité , Polyéthylène glycols/pharmacocinétique , Polyéthylène glycols/toxicité , Acide polyglutamique/pharmacocinétique , Acide polyglutamique/toxicité , Animaux , Cytokines/sang , Systèmes de délivrance de médicaments , Femelle , Fluorescence , Souris de lignée BALB C , Nanocapsules/composition chimique , Spécificité d'organe/effets des médicaments et des substances chimiques , Polyélectrolytes/composition chimique , Polyéthylène glycols/composition chimique , Acide polyglutamique/composition chimique , Rhodamines/composition chimique , Distribution tissulaire , Régulation positive/effets des médicaments et des substances chimiques
19.
J Mater Chem B ; 7(42): 6592-6603, 2019 11 14.
Article de Anglais | MEDLINE | ID: mdl-31589221

RÉSUMÉ

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.


Sujet(s)
Antibactériens/pharmacologie , Fibre de coton , Eugénol/pharmacologie , Nanocapsules/composition chimique , Téréphtalate polyéthylène/composition chimique , Matériaux intelligents/pharmacologie , Antibactériens/composition chimique , Antibactériens/toxicité , Bandages , Carboxylic ester hydrolases/composition chimique , Lignée cellulaire , Cellulase/composition chimique , Fibre de coton/toxicité , Systèmes de délivrance de médicaments , Libération de médicament , Escherichia coli/effets des médicaments et des substances chimiques , Eugénol/composition chimique , Eugénol/toxicité , Fibroïne/composition chimique , Fibroïne/toxicité , Humains , Nanocapsules/toxicité , Téréphtalate polyéthylène/toxicité , Sérum-albumine humaine/composition chimique , Sérum-albumine humaine/toxicité , Matériaux intelligents/composition chimique , Matériaux intelligents/toxicité , Staphylococcus aureus/effets des médicaments et des substances chimiques
20.
Chem Commun (Camb) ; 55(60): 8876-8879, 2019 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-31286121

RÉSUMÉ

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.


Sujet(s)
Antinéoplasiques/pharmacologie , Calixarènes/composition chimique , Camptothécine/pharmacologie , Vecteurs de médicaments/composition chimique , Nanocapsules/composition chimique , Phénols/composition chimique , Antinéoplasiques/composition chimique , Calixarènes/synthèse chimique , Calixarènes/toxicité , Camptothécine/composition chimique , Vecteurs de médicaments/synthèse chimique , Vecteurs de médicaments/toxicité , Libération de médicament , Humains , Concentration en ions d'hydrogène , Cellules MCF-7 , Nanocapsules/toxicité , Phénols/synthèse chimique , Phénols/toxicité
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