Antidiabetic potential of mucilage fraction extracted from Astragalus gyzensis seeds

The objective of the current work is to extract a new mucilage fraction from Astragalus gyzensis Bunge. seeds, which are collected from the El-Oued province (septentrional Algerian Sahara) and evaluated for their antidiabetic potential. The mucilage fraction is obtained using hot water extraction followed by alcoholic precipitation of polysaccharides by cold ethanol (96%). The primary investigation was performed by describing the main structural features of the extract through colorimetric assays, Fourier-transform infrared spectroscopy and thin-layer chromatography analysis using two systems. Biological activity was also monitored by antidiabetic activity by testing the inhibition of α-amylase and α-glucosidase enzymes in vitro. The extraction yield was 20.69%. The chemical composition mainly consisted of 78.60±0.29% carbohydrates, among them 63.92±0.67% neutral sugar, 15.78±0.76% uronic acid, 8.08±0.04% proteins and 2.57±0.05% phenolic compounds. The results obtained by thin-layer chromatography analysis showed the dominance of mannose and galactose. Fourier-transform infrared spectrum showed characteristic bands expected galactomannans. The investigations highlighted the antihyperglycemic effect in a dose-dependent manner by the inhibition of the α-amylase enzyme (IC50=0.8±0.005 mg/mL). These factors make it suitable for the industrial application of dietary supplement fiber made for diabetic individuals. DOI: http://dx.doi.org/10.5281/zenodo.761853

Systèmes polymères stimuli sensibles

International audienceThe polymers can be found in different forms in solution (particles, capsules, pseudo-micelles, hydrogels…) or on surface with important prospects in many field applications. These polymer systems are particularly very good candidates to entrap, transport and deliver an active substance in biomedical applications however with many limitations on control of release of a given target. The stimuli-sensitive polymers, also called smart or environmentally sensitive polymers, present physical or chemical changes under the action of small variations of an external stimulus. This signal acts as a stimulus which causes the change of conformation and/or solvation of the macromolecular chains by modifying their various interactions. The stimuli are classified into two broad categories: physical or external stimuli: temperature, mechanical stress, light, magnetic and electric fields; chemical and biochemical or internal stimuli: pH, ionic strength, chemical molecule (glucose, redox) or biochemical (enzymes, antigens…). The use of stimuli-sensitive pathway is widely used in the literature to enhance or trigger the release of an active compound. In this paper, we present the different stimuli addressing the theoretical aspects, polymers corresponding to these stimuli. Some examples illustrate these systems for the controlled release of active compounds.Les polymères peuvent se trouver sous différentes formes soit en solution (particules, capsules, pseudo-micelles, hydrogels…) soit en surface ouvrant de larges perspectives d’applications dans de nombreux domaines. Ces systèmes polymères sont en particulier de très bons candidats pour piéger, véhiculer puis libérer une substance active dans les applications biomédicales avec cependant de nombreuses limites sur le contrôle de la libération sur une cible donnée. Les polymères stimuli-sensibles, également appelés polymères intelligents ou sensibles à l’environnement, présentent des modifications physiques ou chimiques sous l’action de faibles variations d’un stimulus externe. Ce stimulus agit comme un signal qui entraîne une évolution de la conformation et/ou de la solvatation des chaînes macromoléculaires en modifiant leurs différentes interactions. Les stimuli sont classés en deux grandes catégories : stimuli physiques ou externes : température, contrainte mécanique, lumière, champs magnétiques et électriques ; stimuli chimiques et biochimiques ou internes : pH, force ionique, molécule chimique (glucose, redox) ou biochimique (enzymes, antigènes…). L’utilisation d’un caractère stimuli-sensible est une voie très utilisée dans la littérature pour améliorer voire déclencher la libération d’un composé actif. Dans cet exposé, nous présenterons les différents stimuli en abordant les aspects théoriques et les polymères concernés. Quelques exemples illustreront ces systèmes pour la libération contrôlée de principes actifs

Colloidal Polyelectrolyte Complexes from Hyaluronic Acid: Preparation and Biomedical Applications

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Poly( -caprolactone)-g-alginate: synthèse, caractérisation physico-chimique en solution aqueuse et application à la séquestration et à la libération contrôlée

L objectif de cette étude est de synthétiser un nouveau polysaccharide hydrosoluble amphiphile, par greffage d un polyester hydrophobe, biocompatible et biodégradable, la poly(e-caprolactone) (PCL), sur un polysaccharide anionique, l alginate, via des fonctions ester. La synthèse est réalisée en phase hétérogène (émulsion eau/huile) en présence de tensioactif. Les copolymères amphiphiles (PCL-g-alginate) ont été synthétisés avec des chaînes de PCL de masse molaire variable (530 et 1250 g/mol) et des taux de greffage compris entre 3,5%mol et 15%mol. En solution aqueuse, les PCL-g-alginates ont un comportement classique de polyélectrolyte associatif hydrosoluble. Aux faibles concentrations, les interactions hydrophobes intramoléculaires sont prédominantes (conformations compactes), et au-dessus d une concentration critique, des interactions intermoléculaires hydrophobes s établissent (fort accroissement de viscosité). En milieu salin, le comportement est atypique pour les copolymères obtenus avec la PCL à 530 g/mol avec une forte prédominance d interactions intramoléculaires sur une large gamme de concentrations, tandis qu avec les copolymères à base de PCL 1250 g/mol, nous retrouvons un comportement de pseudo-gel. Ces propriétés originales en milieu salin ont été exploitées par l élaboration d un système à libération contrôlée de principes actifs hydrophobes ou amphiphiles, obtenu par réticulation ionotropique des PCL-g-alginates avec des ions calcium. Les hydrogels obtenus peuvent protéger un principe actif amphiphile (la théophylline) dans un simulacre de fluide gastrique (pH 1,2), et permettent de ralentir sa cinétique de libération dans un simulacre de fluide intestinal (pH 6,8) grâce, notamment, à des interactions hydrophobes entre le principe actif et les microdomaines hydrophobes formés par les PCL-g-alginates. En relation avec l étude physico-chimique en solution saline, la série 530-x présente les meilleures conditions de rétention du principe actif. Les cinétiques de libération peuvent également être fortement ralenties et contrôlées en recouvrant les matrices de PCL-g-alginate/Ca2+ par une membrane de polyélectrolyte à base d un polysaccharide cationique, le chitosane.The aim of this study is to synthesize a new hydrophobically associating water-soluble polysaccharide, prepared by covalent fixation of an hydrophobic, biodegradable and biocompatible polyester, poly(e-caprolactone) (PCL), side chains onto alginate (an anionic polysaccharide) via ester function. Synthesis takes place in heterogeneous media (o/w emulsion) stabilized by a tensioactive. Amphiphilic copolymers (PCL-g-alginate) with two different molar masses of PCL (530 and 1250 g/mol) were synthesized with molar hydrophobe contents ranged from 3.5% to 15%. These new amphiphilic compounds exhibit, in aqueous solution, the typical properties of hydrophobically associating water-soluble polyelectrolytes. At high dilution, data suggest the formation of compact conformations, resulting from intramolecular hydrophobic associations. Above a critical polymer concentration, intermolecular hydrophobic interactions take place and enhance dramatically the viscosity of copolymer solutions. In salt media, nature of hydrophobic interactions depends on the length of PCL chains. For MPCL=530 g/mol, intramolecular hydrophobic interactions are predominant for a wide range of concentration and for longest PCL chains (MPCL=1250 g/mol) strong intermolecular hydrophobic interactions form and can lead to the formation of a pseudo-gel. Finally, a new amphiphilic drug delivery system was obtained by ionotropic gelation of PCL-g-alginate with calcium ions. It was demonstrated PCL-g-alginate hydrogels can protect an amphiphilic drug (theophylline) in simulated gastric fluid (pH 1.2), and slow down its kinetic release in simulated intestinal fluid (pH 6.8) due to hydrophobic interactions between amphiphilic drug and hydrophobic clusters formed by PCL-g-alginate. Results can be correlated with the physico-chemical properties in salt media and 530-x copolymers present a better drug retention. Kinetics release can also be controlled and strongly slow downed by covering the matrices with a polyelectrolyte membrane based on a cationic polysaccharide, chitosan.ROUEN-BU Sciences (764512102) / SudocROUEN-BU Sciences Madrillet (765752101) / SudocSudocFranceF

Hydrogels physiques et chimiques à propriétés amphiphiles à base de polysaccharides aux échelles nano et microscopiques

La synthèse et la caractérisation d hydrogels amphiphiles à base de carboxyméthylpullulane et d un agent réticulent hydrophobe, le dibromohexane, ont fait l objet de ce travail. La cinétique de gélification est rapide et chaque dibromohexane donne un lien de réticulation. Ces hydrogels possèdent deux fractions : une fraction gel et une fraction sol dont les proportions varient avec les paramètres de synthèse. Ces systèmes présentent un caractère métastable en étant très sensibles au temps et à la température pour donner des objets dont les tailles varient de quelques nanomètres à quelques microns. Leur structure est complexe et provient de la création de liens chimiques (irréversibles) mais aussi d associations hydrophobes (réversibles). Une étude préliminaire de séquestration de colorants hydrophobes montre un potentiel intéressant.The aim of this work is the synthesis and the characterization of amphiphilic hydrogels based on carboxymethylpullulan and on a hydrophobic cross-linking agent : the dibromohexan. The kinetics of gelification is fast and every incorporated dibromohexan molecule gives a cross-link. These hydrogels possess two fractions : a gel fraction and a sol fraction whose proportions vary with the synthesis parameters. These systems present a metastable character and are very sensitive to time and temperature to give objects with a size from some nanometers to some micrometers. Their structure is complex and is constituted from chemical crosslinks (irreversible) and hydrophobic associations (reversible). The preliminary study of the entrapment of hydrophobic dyes shows an interesting potential.ROUEN-BU Sciences (764512102) / SudocSudocFranceF

A novel amphiphilic pH-sensitive hydrogel based on pullulan

International audienceNovel polyelectrolyte and amphiphilic hydrogels based on pullulan have been prepared using 1-ethyl-3-[3-(dimethylamino)-propyl]carbodiimide hydrochloride and N-hydroxysuccinimide. The cross-linking reaction is fast and lead to zero length ester cross-links by the reaction of a carboxylate group with an alcohol function of the polysaccharide. The charge density and the hydrophobic rate of the precursor carboxymethylpullulan (CMP) are controlled during the carboxymethylation of pullulan and the grafting reaction of octyl chains on CMP, respectively. The grafting degree influences the conformation of the hydrophobically modified CMP (HMCMP) in solution and leads to the formation of hydrophobic clusters firstly in the HMCMP solutions and further in the HMCMP hydrogels. The swelling measurements of HMCMP hydrogels at different salt concentrations (0–0.2 M NaCl) and different pH (3–11) shows the ionic strength and pH sensitivity of the gels. The loading of a hydrophobic probe molecule can be controlled by the grafting degree of HMCMP hydrogels

Using Targeted Nano-Antibiotics to Improve Antibiotic Efficacy against <i>Staphylococcus aureus</i> Infections

The poor bioavailability of antibiotics at infection sites is one of the leading causes of treatment failure and increased bacterial resistance. Therefore, developing novel, non-conventional antibiotic delivery strategies to deal with bacterial pathogens is essential. Here, we investigated the encapsulation of two fluoroquinolones, ciprofloxacin and levofloxacin, into polymer-based nano-carriers (nano-antibiotics), with the goal of increasing their local bioavailability at bacterial infection sites. The formulations were optimized to achieve maximal drug loading. The surfaces of nano-antibiotics were modified with anti-staphylococcal antibodies as ligand molecules to target S. aureus pathogens. The interaction of nano-antibiotics with the bacterial cells was investigated via fluorescent confocal microscopy. Conventional tests (MIC and MBC) were used to examine the antibacterial properties of nano-antibiotic formulations. Simultaneously, a bioluminescence assay model was employed, revealing the rapid and efficient assessment of the antibacterial potency of colloidal systems. In comparison to the free-form antibiotic, the targeted nano-antibiotic exhibited enhanced antimicrobial activity against both the planktonic and biofilm forms of S. aureus. Furthermore, our data suggested that the efficacy of a targeted nano-antibiotic treatment can be influenced by its antibiotic release profile

Lyophilization for Formulation Optimization of Drug-Loaded Thermoresponsive Polyelectrolyte Complex Nanogels from Functionalized Hyaluronic Acid

International audienceThe lyophilization of nanogels is practical not only for their long-term conservation but also for adjusting their concentration and dispersant type during reconstitution for different applications. However, lyophilization strategies must be adapted to each kind of nanoformulation in order to minimize aggregation after reconstitution. In this work, the effects of formulation aspects (i.e., charge ratio, polymer concentration, thermoresponsive grafts, polycation type, cryoprotectant type, and concentration) on particle integrity after lyophilization and reconstitution for different types of polyelectrolyte complex nanogels (PEC-NGs) from hyaluronic acid (HA) were investigated. The main objective was to find the best approach for freeze-drying thermoresponsive PEC-NGs from Jeffamine-M-2005-functionalized HA, which has recently been developed as a potential platform for drug delivery. It was found that freeze-drying PEC-NG suspensions prepared at a relatively low polymer concentration of 0.2 g.L−1 with 0.2% (m/v) trehalose as a cryoprotectant allow the homogeneous redispersion of PEC-NGs when concentrated at 1 g.L−1 upon reconstitution in PBS without important aggregation (i.e., average particle size remaining under 350 nm), which could be applied to concentrate curcumin (CUR)-loaded PEC-NGs for optimizing CUR content. The thermoresponsive release of CUR from such concentrated PEC-NGs was also reverified, which showed a minor effect of freeze-drying on the drug release profile

Hydrogels à base de xanthane (effet de la conformation des chaînes macromoléculaires)

Des hydrogels chimiques à base de xanthane ont été élaborés en jouant sur les conditions de synthèse pour se placer dans des milieux favorables aux deux conformations possibles du xanthane : ordonnée (double hélice) et désordonnée (pelote statistique). Une grande partie du travail a été consacrée à la détermination des paramètres contrôlant la transition conformationnelle hélice - pelote du xanthane en solutions concentrées. Ceux-ci ont été optimisés en vue de la synthèse des hydrogels à base de xanthane en milieu acide par l'acide adipique dihydrazide (ADH) et basique par le trisodium trimetaphosphate (STMP). Les systèmes sont caractérisés par analyse élémentaire, taux de gonflement et comportement dans différentes conditions du milieu. Quelques molécules modèles ont été testées afin de connaître leur potentiel de retenir et de libérer les principes actifs dans des milieux qui imitent les fluides humains.Chemical hydrogels based on xanthan have been synthesized with different conditions that are favorable to the two possible xanthan conformation : ordered (double helix) disordered (statistic coil). A great part has been devoted the determination of parameters which controlled the conformation transition in xanthan concentrated solutions. Theses parameters have been optimized in view to synthetize xanthan hydrogels in acidic medium by adipic acid dihydrazid (ADH) and in alkaline medium by trisodium trimetaphosphate (STMP). The systems are characterized by elemental analysis, kinetic swelling degree and behavior in different environnmental conditions. Some model molecules have been tested in order to assess the entrapping and releasing properties in environments that are mimicking human fluids.ROUEN-BU Sciences (764512102) / SudocSudocFranceF

Thermosensitive nanocarriers for drug delivery from polyelectrolyte complexes of hyaluronic acid grafted with PEO PPO: old polymers, new combination

International audienceColloidal polyelectrolyte complexes (PECs) from hyaluronic acid (HA) have received increasing attention recently as simple-to-prepare but highly robust drug delivery systems (DDS) with the advantages of nanomedicine, green chemistry and the inherent properties of HA, i.e. excellent biocompatibility, biodegradability and selective biological interactions. Meanwhile, poly(ethylene oxide)-co-poly(propylene oxide) (PEO-PPO) is a classical thermosensitive copolymer widely employed in thermoresponsive biomedical materials. Despite the well-known advantages of these polymers, there has so far been no nanoparticulate DDS reported from PEO-PPO-grafted HA. In our work, a novel type of hybrid nanoparticulate system has been developed from PECs of HA grafted with Jeffamine® M-2005 (M2005), a commercialized amine-terminated PEO-PPO, electrostatically complexed with diethylaminoethyl dextran (DEAE-D) or poly-L-lysine (PLL), which are common polycations in biomedical fields. It was revealed that the presence of M2005 grafts as well as their thermoresponsiveness leads to a series of interesting properties of PEC nanocarriers, including high stability against physiological salinity, thermo-controllable drug encapsulation, thermo-triggered drug release, better-preserved particle size after lyophilization, and transformability into more compact and long-term stable polymeric nanoparticles using autoclave. PLL was also found to be more beneficial than DEAE-D in terms of particle stability and drug encapsulation, rendering HA-M2005/PLL PECs the most promising among the investigated systems. These findings not only provide a better insight into the physicochemical properties of PECs but also highlight the potential of thermoresponsive PECs based on PEO-PPO-grafted HA as a very new concept of hybrid material from already well-known polymers for drug delivery