117 research outputs found
Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders
No full textHyaluronic acid (HA) is a Glycosaminoglycan made of disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. Its molecular mass can reach 10 MDa and its physiological properties depend on its polymeric property, polyelectrolyte feature and viscous nature. HA is a ubiquitous compound found in almost all biological tissues and fluids. So far, HA grades are produced by biotechnology processes, while in the human organism it is a major component of the extracellular matrix (ECM) in brain tissue, synovial fluid, vitreous humor, cartilage and skin. Indeed, HA is capable of forming hydrogels, polymer crosslinked networks that are very hygroscopic. Based on these considerations, we propose an overview of HA-based scaffolds developed for brain cancer treatment, central and peripheral nervous systems, discuss their relevance and identify the most successful developed systems
Polymer-lipid hybrid nanomedicines to deliver siRNA in and against glioblastoma cells
No full textSmall interfering RNA (siRNA) holds great potential to treat many difficult-to-treat diseases, but its delivery remains the central challenge. This study aimed at investigating the suitability of polymer-lipid hybrid nanomedicines (HNMeds) as novel siRNA delivery platforms for locoregional therapy of glioblastoma. Two HNMed formulations were developed from poly(lactic-co-glycolic acid) polymer and a cationic lipid: 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 3 ss-[N-(N' ,N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol). After characterization of the HNMeds, a model siRNA was complexed onto their surface to form HNMed/siRNA complexes. The physicochemical properties and siRNA binding ability of complexes were assessed over a range of nitrogen-to-phosphate (N/P) ratios to optimize the formulations. At the optimal N/P ratio of 10, complexes effectively bound siRNA and improved its protection from enzymatic degradation. Using the NIH3T3 mouse fibroblast cell line, DOTAP-based HNMeds were shown to possess higher cytocompatibility in vitro over the DCChol-based ones. As proof-of-concept, uptake and bioefficacy of formulations were also assessed in vitro on U87MG human glioblastoma cell line expressing luciferase gene. Complexes were able to deliver anti-luciferase siRNA and induce a remarkable suppression of gene expression. Noteworthy, the effect of DOTAP-based formulation was not only about three-times higher than DC-Chol-based one, but also comparable to lipofectamine model transfection reagent. These findings set the basis to exploit this nanosystem for silencing relevant GB-related genes in further in vitro and in vivo studies
Interactions de nanovecteurs d'agents anticancéreux avec le milieu vivant et franchissement de barrières biologiques
No full textThe extracellular matrix glycoprotein Tenascin-C is expressed by oligodendrocyte precursor cells and required for the regulation of maturation rate, survival and responsiveness to platelet-derived growth factor
No full textAnalysis of Tenascin-C (TN-C) knockout mice revealed novel roles for this extracellular matrix (ECM) protein in regulation of the developmental programme of oligodendrocyte precursor cells (OPCs), their maturation into myelinating oligodendrocytes and sensitivity to growth factors. A major component of the ECM of developing nervous tissue, TN-C was expressed in zones of proliferation, migration and morphogenesis. Examination of TN-C knockout mice showed roles for TN-C in control of OPC proliferation and migration towards zones of myelination [E. Garcion et al. (2001) Development, 128, 2485-2496]. Extending our studies of TN-C effects on OPC development we found that OPCs can endogenously express TN-C protein. This expression covered the whole range of possible TN-C isoforms and could be strongly up-regulated by leukaemia inhibitory factor and ciliary neurotrophic factor, cytokines known to modulate OPC proliferation and survival. Comparative analysis of TN-C knockout OPCs with wild-type OPCs reveals an accelerated rate of maturation in the absence of TN-C, with earlier morphological differentiation and precocious expression of myelin basic protein. TN-C knockout OPCs plated on poly-lysine displayed higher levels of apoptosis than wild-type OPCs and there was also an earlier loss of responsiveness to the protective effects of platelet-derived growth factor (PDGF), indicating that TN-C has anti-apoptotic effects that may be associated with PDGF signalling. The existence of mechanisms to compensate for the absence of TN-C in the knockout is indicated by the development of oligodendrocytes derived from TN-C knockout neurospheres. These were present in equivalent proportions to those found in wild-type neurospheres but displayed enhanced myelin membrane formation
Analisi didattica di una situazione di apprendimento particolare nella scuola dell’infanzia francese: i rituali del mattino
No full textDieser Beitrag verfolgt eine doppelte Zielsetzung: aufzuzeigen, welche Art von Lernsituationen die französischen Kindergarten-Lehrkräfte mit den Morgenritualen schaffen, um das Lernen der Kinder anzuregen, sowie zu zeigen, dass diese spezifischen Unterrichtssituationen mit Konzepten, die der Mathematikdidaktik entstammen, insbesondere jenem des Lernmilieus, analysiert werden können. Die Morgenrituale im Kindergarten erlauben es Lehrpersonen und Kindern, gemeinsam Lernsituatioen aufzubauen, indem durch die Dialektik von Bekanntem und Neuem eine stabile Situation geschaffen wird. In diesem Rahmen lernen die Kinder zwar nicht Lesen und Rechnen, aber sie lernen die Funktion und den Wert der Kulturtechniken kennen, bevor sie sich diese in der Primarschule aneignenThis article has two objectives:
– to show which type of situation the teachers in French nursery schools set up in order that the pupils learn in this school,– to show that these particular situations can be analyzed with the concepts resulting from mathematical didactics, in particular that of «milieu for study».
By building a stable «milieu», the morning ritual in nursery schools allows the teachers and the pupils to co-build a «milieu for study». However, within this framework, the pupils learn neither how to read, nor to calculate. They learn how to use the tools of our society in which we live. This is done before studying these same tools at the elementary school level.Cet article poursuit un double objectif: décrire quel type de situations les enseignantes de l’école maternelle française mettent en place pour que dans cette école les élèves apprennent,montrer que ces situations particulières peuvent être analysées avec les concepts issus de la didactique des mathématiques, notamment celui de milieu pour l’étude.En construisant un milieu stable, tout en faisant fonctionner la dialectique ancien/nouveau, les rituels du matin à l’école maternelle permettent au maître et aux élèves de co-construire un milieu pour apprendre. Cependant, dans ce cadre, les élèves n’apprennent ni à lire, ni le fonctionnement de la numération; ils apprennent à utiliser les outils de la société dans laquelle nous vivons avant d’étudier ces mêmes outils comme objets, à l’école élémentaire.Queste articolo persegue un doppio obiettivo: mostrare che tipo di situazioni vengono create da parte degli insegnanti della scuola dell’infanzia francese affinché i bambini possano imparare e illustrare come queste situazioni possano essere analizzate con degli strumenti concettuali derivati dalla didattica della matematica. Facendo capo alla dialettica vecchio-nuovo, i rituali mattinieri permettono all’insegnante e agli allievi di realizzare in comune un ambiente di apprendimento stabile. Ciònondimeno in un contesto del genere i bambini non imparano a leggere o a far di conto ma piuttosto ad utilizzare gli strumenti sociali prima affrontarli come oggetti di apprendimento vero e proprio alla scuola elementare
Iron metabolism: a double-edged sword in the resistance of glioblastoma to therapies
No full textGlioblastoma (GBM), the deadliest primary tumor of the central nervous system (CNS), is a clear illustration of the resistance of cancer cells to conventional therapies. Application of combinatorial strategies able to overcome pivotal factors of GBM resistance, particularly within the resection margins, represents an essential issue. This review focuses on the role of iron metabolism in GBM progression and resistance to therapy, and the impact of its pharmaceutical modulation on the disease. Iron, through its involvement in many biological processes, is a key factor in the control of cell behavior and cancer biology. Therefore, targeting cellular iron signaling or taking advantage of its dysregulation in cancer cells may lead to new opportunities for improving treatments and drug delivery in GBM
Reciprocal competition between lipid nanocapsules and P-gp for paclitaxel transport across Caco-2 cells.
No full textBiopharmaceutical parameters to concider in order to alter the fate of nanocarriers after oral delivery.
No full textLipid nanocarriers improve paclitaxel transport throughout human intestinal epithelial cells by using vesicle-mediated transcytosis
No full textThe use of lipid nanocapsules (LNCs) has enabled an improvement of the oral bioavailability of paclitaxel (Ptx). However, mechanisms that support this recent observation are not yet understood. By focusing on the well defined in vitro Caco-2 model, the purpose of this study was to evaluate the transport of LNCs across a model intestinal barrier. Firstly, four sizes of paclitaxel or dye (Nile Red)-loaded LNCs were formulated and LNCs with sizes between 26.3+/-2.7nm and 132.7+/-5.5nm were obtained. Different transport and uptake experiments were then performed across a Caco-2 cells culture model using these LNCs. Paclitaxel-loaded LNCs improved permeability of Ptx across intestinal epithelium compared with free Ptx or Taxol((R)) by a factor of 3.5. At 37 degrees C particle size did not influence transport efficiency. However, at 4 degrees C a decrease in Ptx transport was observed with increasing size of LNCs. Thus, with LNCs of 25nm size, the apparent permeability coefficient (P(app)) was 5.3+/-1.1cm s(-1) at 37 degrees C and 2.2+/-0.4cm s(-1) at 4 degrees C. In comparison in LNCs of 130nm size, the P(app) decreased from 5.8+/-0.8cm s(-1) at 37 degrees C to 0.5+/-0.1cm s(-1) at 4 degrees C. The uptake of LNCs by Caco-2 cells and the incapacity of LNCs to open tight junctions were also demonstrated. Furthermore, experiment transports were performed in the presence of different inhibitors of endocytosis. Findings indicated a reduction of Ptx transport of 30+/-6% when cell cholesterol was depleted, 65+/-12% when caveolae-mediated endocytosis was inhibited and 20+/-8% when clathrin-mediated endocytosis was inhibited. Finally, transmission electronic microscopy showed the presence of nano-objects on the basolateral side of the Caco-2 cell monolayers when LNCs were applied on the apical side
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