Littérature scientifique sur le sujet « Nanocapsules – Toxicologie »

abstract A simple stability-indicating RP-HPLC/UV method was validated for determination of beclomethasone dipropionate (BD) in nanocapsule suspensions. Chromatographic conditions consisted of a RP C18column (250 mm x 4.60 mm, 5 µm, 110 Å), using methanol and water (85:15 v/v) as mobile phase at 1.0 mL/min with UV detection at 254 nm. The calibration curve was found to be linear in the concentration range of 5.0-25.0 µg/mL with a correlation coefficient > 0.999. Precision was demonstrated by a relative standard deviation lower than 2.0%. Accuracy was assessed by the recovery test of BD from nanocapsules (98.03% to 100.35%). Specificity showed no interference from the components of nanocapsules or from the degradation products derived from acid, basic and photolytic conditions. In conclusion, the method is suitable to be applied to assay BD in bulk drug and in nanocapsules, and it can be employed to study stability and degradation kinetics.

Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules and nanospheres, which are distinguished by the morphological structure. Polymeric NPs have shown great potential for targeted delivery of drugs for the treatment of several diseases. In this review, we discuss the most commonly used methods for the production and characterization of polymeric NPs, the association efficiency of the active compound to the polymeric core, and the in vitro release mechanisms. As the safety of nanoparticles is a high priority, we also discuss the toxicology and ecotoxicology of nanoparticles to humans and to the environment.

The ever-increasing accomplishment of Nanotechnology in Science has raised the prospects of improving the properties and usability of an array of substances, minimizing the negative impact on human health as well as the environment. In the context of human health, continuous research is going on to obtain the maximum benefit of a pharmaceutical compound with a minimum dose by improving its delivery to the target site. Nanotechnology plays a key role in drug delivery providing target-oriented better therapeutic efficiency with minimal adverse effects. The widespread application potential of polymeric nanocapsules in drug delivery, diagnostics, biomedical imaging, and other related domains has made them one of the most extensively studied nanomaterials. Owing to their biocompatibility and biodegradability, much research has been dedicated to exploring the drug delivery aspect of polymeric nanocapsules. Several technological strategies have been developed in the last decade to improve the production protocol and choose appropriate materials to produce nanocapsules for superior performances. Polymeric nanocapsules are advantageous because of their excellent control over the release rate and modulation of the pharmacokinetic properties of various active ingredients.

Abstract The present work deals with the production of nanocapsules containing a natural corrosion inhibition component. Azadirachta indica was encapsulated in urea-formaldehyde polymeric shell using ultrasound-assisted and conventional approaches of in situ polymerization. Subsequently nanocapsules were incorporated into clear epoxy polyamide to develop the green self-healing corrosion inhibition coating. The actual performance of the coating was evaluated based on the studies involving the repair of the crack of high solid surface coating. Corrosion inhibition of the healed area has been evaluated using the electrochemical impedance spectroscopy and immersion test based on the use of standard epoxy coating. The obtained results confirmed better corrosion protection in terms of the electrochemical impendence spectroscopy data and Tafel plot. It was found that current density decreases from 0.0011 A/cm2 (for standard epoxy coating) to 5.22 E−7 A/cm2 as 4 wt% nanocapsules incorporated in coating.

A simple, rapid, and sensitive fluorimetric method was developed and validated to quantify curcumin in lipid and polymeric nanocapsule suspensions, using acetonitrile as a solvent. The excitation and emission wavelengths were set at 397 nm and 508 nm, respectively. The calibration graph was linear from 0.1 to 0.6 µg/mL with a correlation coefficient of 0.9982. The detection and quantitation limits were 0.03 and 0.10 µg/mL, respectively. The validation results confirmed that the developed method is specific, linear, accurate, and precise for its intended use. The current method was successfully applied to the evaluation of curcumin content in lipid and polymeric nanocapsule suspensions during the early stage of formulation development.

In parenteral nutrition, the lipid emulsions are usually presented separately from other components. The admixture is made just before or during administration because of limited stability. The purpose of the present study is the formulation of lipid nanocapsules (LNC) based on Argan-oil and their introduction into preparations for parenteral nutrition, then the evaluation of their stability. The lipid nanocapsules have been prepared according to the phase inversion temperature method. The experimental design was used to determine the feasibility of LNC with Argan oil (A.O.-LNC), the evaluation of their size and the stability in the final mixing parenteral nutrition. The average size of the LNC was chosen as a response. The LNC based on 14% Argan oil, 6% Labrafac ®, 55% water and 25% of Solutol ® with an average size of 44 nm was selected for the preparation of the parenteral nutrition. The particle size distribution with a value of 70 nm and a polydispersity index of 0.102 indicates the homogeneity of the populations of particles. The statistical analysis shows the excellent stability of parenteral nutrition for 14 days.

The intention of the current work was to develop and optimize the formulation of biodegradable polymeric nanocapsules for lamivudine (LMV) in order to obtain desired physical characteristics so as to have improved liver targetability. Nanocapsules were prepared in this study as aqueous-core nanocapsules (ACNs) with poly(lactide-co-glycolide) using a modified multiple emulsion technique. LMV was taken as a model drug to investigate the potential of ACNs developed in this work in achieving the liver targetability. Three formulations factors were chosen and 33 factorial design was adopted. The selected formulation factors were optimized statistically so as to have the anticipated characteristics of the ACNs viz. maximum entrapment efficiency, minimum particle size, and less drug release rate constant. The optimized LMV-ACNs were found to have 71.54 ± 1.93% of entrapment efficiency and 288.36 ± 2.53 nm of particle size with zeta potential of −24.7 ± 1.2 mV and 0.095 ± 0.006 h−1 of release rate constant. This optimized formulation was subjected to surface modification by treating with sodium lauryl sulphate (SLS), which increased the zeta potential to a maximum of −41.6 ± 1.3 mV at a 6 mM concentration of SLS. The results of in vivo pharmacokinetics from blood and liver tissues indicated that hepatic bioavailability of LMV was increased from 13.78 ± 3.48 μg/mL ∗ h for LMV solution to 32.94 ± 5.12 μg/mL ∗ h for the optimized LMV-ACNs and to 54.91 ± 6.68 μg/mL ∗ h for the surface-modified LMV-ACNs.

Afin d’augmenter l’efficacité des principes actifs tout en diminuant leurs effets secondaires, beaucoup de recherches sont menées afin d’élaborer un vecteur permettant d’encapsuler des PAs et de les libérer à un endroit précis de l’organisme. Pour cela, il est nécessaire de concevoir un vecteur répondant à un cahier des charges strict. Le vecteur doit permettre le ciblage de la zone à traiter, être stable in vivo avant la libération du principe actif, biocompatible et non-toxique. Dans ce contexte, nous nous sommes donc fixés comme objectif de préparer et caractériser une famille de vecteurs nanoparticulaires constitués de polymères fonctionnels dégradables appartement à la même famille. Nous avons donc synthétisé de façon simple et reproductible six polymères fonctionnels dérivés du poly(acide malique), polymère reconnu comme biocompatible, dégradable et non toxique : deux polymères hydrophobes, les PMLABe et PMLAHe, quatre copolymères amphiphiles PEGylés, les PEG42-b-PMLABe , PEG42-b-PMLAHe, Biot-PEG62-b-PMLABe et Biot-PEG62-b-PMLAHe. A partir de ces matériaux, nous avons préparé par nanoprécipitation les nanoparticules correspondantes. La taille de ces nanoparticules varie entre 50 et 130 nm avec des indices de polydispersité très faibles. Des études de cytotoxicité in vitro ont montré que toutes les nanoparticules préparées étaient non toxiques. D’autre part, nous avons montré qu’il était possible d’encapsuler jusqu’à 30wt% de doxorubicine et que cette dernière conservait son efficacité in vitro. Enfin, des études in vitro à l’aide de nanoparticules encapsulant une sonde de fluorescence ont permis de montrer que la présence du ligand de ciblage biotine permettait d’augmenter la capture cellulaire des nanoparticules PEGylées ciblantes
To increase the effectiveness of drugs while reducing side effects, much research is being conducted to develop a vehicle which will be able to encapsulate drugs and release them at a specific site in the body. For this, it is necessary to design a vehicle that meets strict specifications. The vector should allow targeting of the treatment area, be stable in vivo before the release of the drug, non-toxic and biocompatible. In this context, we consider to prepare and characterize a family of nanoparticles made of degradable functional polymers belonging to the same family. We therefore synthesized, in a simple and reproducible way, six functional polymers derived from poly(malic acid), which is recognized as a biocompatible, degradable and nontoxic polymer: two hydrophobic polymers, the PMLABe and PMLAHe, and four PEGylated amphiphilic copolymers, the PEG42-b-PMLABe, PEG42-b-PMLAHe, Biot-PEG62-b-PMLABe and Biot-PEG62-b-PMLAHe. Starting from these materials, we prepared by nanoprecipitation the corresponding nanoparticles. The size of these nanoparticles ranges from 50 to 130 nm with very low polydispersity indices. In vitro cytotoxicity studies have shown that all the prepared nanoparticles were non-toxic. On the other hand, we have shown that it was possible to encapsulate up to 30wt% of doxorubicin and that this drug retained its efficacy in vitro. Finally, in vitro studies using fluorescent probe loaded nanoparticles have shown that the presence of the targeting ligand, biotin, increased the cellular uptake of PEGylated targeting nanoparticles

Ce travail doctoral s’articule autour de l’étude de la biodistribution et la toxicité cellulaire de nanovecteurs : les nanocapsules lipidiques (NCLs). Les paramètres physico-chimiques (la taille, la charge et la pégylation) peuvent influencer les interactions cellulaires. Les NCLs possèdent un fort tropisme hépatique, ce qui a orienté les premiers travaux de recherche sur l’étude des interactions entre des NCLs de 50 et 100 nm et les hépatocytes, représentés par les cellules HepG2 et HepaRG. Une toxicité hépatique relativement faible,concentration, taille et temps dépendante a été démontrée. Les NCLs de 50 nm, pourtant internalisées plus lentement, entraînent une plus grande toxicité, particulièrement sur des cellules cancéreuses (lignée HepG2). L’exposition aux NCLs a généré de la peroxydation lipidique et une mort cellulaire via la ferroptose. Une toxicité plus importante a été observée après 2 semaines (vs. 24 h) et 4 semaines d’exposition(vs. 2 semaines) pour les NCLs de 50 nm. Les NCLs de 100 nm, quant à elles, semblent moins toxiques car la toxicité observée entre 2 et 4 semaines n’augmente pas. Une seconde étude a permis de mieux caractériser les effets de taille et de pégylation, paramètres modifiés pour jouer sur la furtivité sanguine et hépatique. Les NCLs de 50 et 100 nm, pégylées ou non, ont été exposées à du sang humain (ex vivo) afin d’étudier la biodistribution sanguine. Les phagocytes circulants (monocytes et neutrophiles) internalisent rapidement les NCLs, sans infuence de la taille ni de la pégylation. Une évaluation in vitro est venue compléter les données de distribution dans les différentes cellules hépatiques (lignée endothéliale, macrophages humains et hépatocytes). Il a été confirmé que les NCLs se distribuent préférentiellement dans les cellules cancéreuses hépatiques (vs. cellules différenciées) ainsi que dans les macrophages primaires humains et les cellules endothéliales. A l’exception des macrophages humains, une augmentation de la taille des NCLs améliore l’internalisation tandis que la pégylation la diminue. Enfin, les NCLs ne semblent pas immunoactivatrices. En conclusion, la distribution passive dans les cellules hépatiques cancéreuses, associée à une forte toxicité, ainsi que la bonne tolérance avec les autres cellules étudiées (hépatique in vitro et sanguine ex vivo), suggèrent un potentiel intérêt des NCLs dans le traitement de l’hépatocarcinome
This PhD thesis evaluates the biodistribution and cellular toxicity of nanovectors: the lipid nanocapsules (LNCs). Physico-chemical parameters (size, charge and surface coating) can influence cellular interaction. The strong hepatic tropism of LNCs guided the first study on the evaluation of interactions between LNCs, with a diameter of 50 and 100 nm, and hepatocytes, represented by HepG2 and HepaRG cells. A relatively weak toxicity, concentration, size and time dependent was demonstrated. The 50 nm LNCs, although slower to be internalized than 100 nm ones, exhibited a higher toxicity, notably on cancer cells (HepG2 cell line). Exposure to LNCs generated lipid peroxidation which led to cells death via ferroptosis. A higher toxicity has been observed after 2 (vs. 24 h) and 4 weeks of exposure (vs. 2 weeks) for 50 nm LNCs. The 100 nm LNC seemed to be less toxic because their cytotoxicity did not increase between 2 and 4 weeks of exposure. A 2nd study allowed us to better characterized the influence of size and pegylation,parameters modified to improve blood and hepatic stealthness. LNCs of 50 and 100 nm, pegylated or not, have been exposed to human blood (ex vivo) in order to analyze the blood distribution. Circulating phagocytes (monocytes and neutrophiles) quickly internalized LNCs, without influence of size nor pegylation. An in vitro assessment was performed in order to complete the biodistribution study in hepatic cells (endotelial cell line, human macrophages and hepatocytes). It has been confirmed that LNCs preferentially distributed in liver cancer cells (vs. differentiated ones), as well as in primary human macophages and endotelial cells. Except for human macrophages, an increase in size improved internalization whereas pegylation decreased it. Finally, LNCs dit not seem to be immunomodulators. In conclusion, the passive distribution into liver cancer cells, associated with a high cytotoxicity, and the good tolerance observed with the other cells studied (hepatic in vitro and in blood ex vivo), suggest that LNCs could be considered as vectors for hepatocarcinoma treatment

Les nanocapsules lipidiques (NCL) sont une formulation sans solvant permettant d'encapsuler des principes actifs liposolubles comme le paclitaxel. Leurs propriétés sont : taille inférieure à 150 nanomètres (nm), concentration passive dans les tumeurs par effet « Enhanced Permeability and Retention » et inhibition de la glycoprotéine-P, impliquée dans un mécanisme de résistance au paclitaxel. Ce travail a d'abord étudié les adaptations à appliquer à la formulation usuelle des NCL de paclitaxel de 50 nm en vue de réaliser les premiers lots précliniques. Une méthode de conservation par congélation des NCL de paclitaxel dans leur phase aqueuse pendant au moins 6 mois est proposée. La toxicité systémique des lots précliniques de NCL a été étudiée selon la méthode d'Irwin. Les doses maximales tolérées et doses létales 50 du Taxol® et des NCL de paclitaxel sont respectivement de 12 et 19,5 mg/kg et de 96 et 216 mg/kg. Aucune toxicité n'est observée avec des NCL sans paclitaxel. Les NCL de paclitaxel sont plus efficaces que le Taxol® sur un modèle tumoral sous-cutané de la lignée humaine H460. Ce schéma d'administration n'induit aucune toxicité significative. La nébulisation des NCL pour un usage expérimental chez l'animal ou thérapeutique chez l'homme est possible respectivement au moyen d'un Microsprayer® ou d'un nébuliseur eFlow®rapid. Les NCL de paclitaxel de 50 nm ont permis d'optimiser l'effet cytotoxique du paclitaxel en s'affranchissant de la toxicité du Taxol®. Il est possible de générer des aérosols de NCL de paclitaxel. Ces données permettent de poursuivre les études toxicologiques et d'efficacité des NCL administrées par voie systémique et par voie pulmonaire.