Structural characterization and rheological properties of a galactomannan from Astragalus gombo Bunge seeds harvested in Algerian Sahara.

A water soluble polysaccharide (WSP) was extracted and purified from Astragalus gombo seeds (Fabaceae) harvested in Septentrional Sahara (Ouargla, Algeria) with a yield of 6.8% (w/w of the dry seed ground). It was characterized by gas chromatography coupled to the mass spectrometry (GC-MS), size exclusion chromatography with Multi-Angle Light Scattering analysis (SEC-MALLS), high-resolution 1H and 13C NMR, and rheological measurements. The structural characterization indicated that this WSP fraction is a galactomannan with a mannose/galactose ratio of 1.7 formed by a backbone of ß-(1,4)-d-mannopyranosyl residues (63%) substituted at O-6 position by a single α-galactopyranose residue (37%). SEC-MALLS analysis revealed that this galactomannan has an average molecular mass (Mw) of 1.1×106g/mol, an intrinsic viscosity of 860mL/g and, a random coil conformation structure. Rheological analysis in semi diluted regimes shown pseudo-plastic and viscoelastic behaviour.

[Stimuli-sensitive polymer systems]. / Systèmes polymères stimuli sensibles.

The 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.

Preparation and characterization of anionic pullulan thermoassociative nanoparticles for drug delivery.

Thermoassociative nanoparticles were obtained through the crosslinking reaction of periodate oxidized carboxymethyl pullulan with two difunctional Jeffamines: ED-600 and ED-2003. The nanoparticles were characterized through (1)H NMR spectra; their particle size, determined by dynamic light scattering (DLS) presented a bimodal distribution, with dimensions varying as a function of amount and type of crosslinking agent used; transmission electron microscopy photos confirmed the spherical shape of the nanoparticles and their dimensions determined by DLS. Their amphiphilic character was evidenced by retention of the dyes: hydrophobic (Rose Bengal), amphiphilic (Brilliant Blue) and hydrophilic (Vitamin B12). The thermosensitive properties, more pronounced for ED-2003 crosslinked nanoparticles, were evidenced through absorbance variation, fluorescence and DLS measurements as a temperature function. The nanoparticles retain important amounts of anionic (diclofenac: 40-80 mg/g), cationic (methylene blue: 70-125 mg/g) and hydrophobic (alpha-tocopherol: 220-350 mg/g) drugs. The in vitro characterization of the drug-polymer conjugates recommends the synthesized nanoparticles as supports for drug delivery.

Collagen functionalized with unsaturated cyclic anhydrides-interactions in solution and solid state.

Maleic anhydride (CMA) and itaconic anhydride modified collagen (CITA) were prepared as precursors for production of interpenetrated polymer networks (IPN). Calculated values for Huggins coefficient in aqueous diluted and semi-diluted solutions of modified collagen indicated a slightly tendency of aggregation for itaconic anhydride-modified collagen. In semi-diluted solution collagen (Coll) and CMA present slightly differences in the thixotropic behavior, while CITA has a pronounced thixotropic behavior. Flow and oscillatory measurements revealed an elastic behavior of the collagen solutions, pure and modified with MA or ITA, as the storage modulus (G') has always a superior value compared with the loss modulus (G″). The denaturation temperature (Td) of unmodified collagen increased from 34°C to 40°C for CMA and to 39°C for CITA respectively, by formation of covalent bonds that stabilize the triple helix.

Effect of chitosan coating on the swelling and controlled release of a poorly water-soluble drug from an amphiphilic and pH-sensitive hydrogel.

In the present work, a new particulate controlled release system was prepared, by coating alginate-g-PCL/Ca(2+) beads with chitosan. The swelling behaviour and controlled release of a poorly water-soluble drug (theophylline) model were studied in media of varying pH, by simulating human fluids at 37 degrees C. In a simulated gastric fluid (SGF, pH 1.2), coated beads presented weak swelling (8-22%) and weak release rates (24-32% within 120min), and were able to protect the drug from this harsh environment. In a simulated intestinal fluid (SIF, pH 6.8), the swelling rates of amphiphilic beads (before disintegration) were strongly reduced (300-1100%) comparatively with those of uncoated beads (700-1700%). This can be explained by the strong electrostatic interactions between the amino groups of chitosan and the carboxylate groups of alginate-g-PCL, leading to the formation of a protective membrane of strong polyelectrolyte complex around the beads. This outermost layer effectively promoted the stability of beads under gastro-intestinal tract conditions, while the hydrophobic interactions between theophylline and PCL grafts allowed a considerable slowing down of the drug release. It was found out that combination of the protective effect of the polyelectrolyte membrane in SIF associated with the hydrophobicity of PCL grafts allowed to release a poorly water-soluble drug, in a controlled manner, for 7h, along a simulated gastro-intestinal tract.

New amphiphilic and pH-sensitive hydrogel for controlled release of a model poorly water-soluble drug.

This paper presents the development of new pH-sensitive, amphiphilic and biocompatible hydrogels based on alginate-g-PCL, cross-linked with calcium ions to form beads, prepared for controlled delivery of poorly water-soluble drug. We have focused our study on the effect of the length of PCL chains (530 and 1250 g mol(-1)). Swelling profiles obtained clearly indicated that these hydrogels swell slightly (10-14%) in a simulated gastric fluid (pH 1.2), and strongly (700-1300% before disintegration) in a simulated intestinal fluid (pH 6.8). In both media, rates of swelling were lower for beads based on amphiphilic derivatives than for alginate/Ca2+ ones due to the hydrophobic PCL grafts, and decreased when hydrophobic character increased. A model drug, theophylline, was entrapped into these hydrogels and release studies were carried out. The drug was protected in acidic fluid (only 14-20% of release for alginate-g-PCL hydrogel against 35% of release for alginate hydrogel during 350 min). The drug is released completely in neutral fluid due to ion exchanges and disintegration of the hydrogel. PCL leads to decrease in the release kinetics in SIF (2h for alginate-g-PCL/Ca2+ beads against 1h for alginate/Ca2+ beads). It was demonstrated that the establishment of clusters inside beads by intramolecular interactions between PCL grafts of 530 g mol(-1) in salt media allowed to retain the drug and to slow down its release considerably.

Collagens, stromal cell-derived factor-1alpha and basic fibroblast growth factor increase cancer cell invasiveness in a hyaluronan hydrogel.

OBJECTIVE: Beyond to control of cell migration, differentiation and proliferation, the extracellular matrix (ECM) also contributes to invasiveness of human cancers. As the roles of hyaluronan (HA) and collagens in this process are still controversial, we have investigated their involvement in cancer pathogenesis. MATERIALS AND METHODS: With this aim in view, we developed a three-dimensional matrix, as reticulate HA hydrogel alone or coated with different collagens, in which cells could invade and grow. RESULTS: We show that cancer cells, which were non-invasive in a single HA hydrogel, acquired this capacity in the concomitant presence of type I or III collagens. Both types of ECM compound, HA and collagens, possess the capacity to stimulate production of metalloprotease-2, recognized otherwise as a factor for poor cancer prognosis. HA-provoked cellular invasiveness resulted from CD44-mediated increase in cytosolic [Ca2+] and its subsequent hydrolysis due to ADAM (a disintegrin and metalloprotease) proteolytic activity. Interestingly, this mechanism seemed to be absent in non-invasive cancer cell lines. CONCLUSION: Furthermore, using basic fibroblast growth factor and stromal cell-derived factor-1alpha, we also show that this three-dimensional reticulate matrix may be considered as a valuable model to study chemokinetic and chemotactic potentials of factors present in tumour stroma.

Synthesis and physicochemical characterization of a novel ampholytic pullulan derivative with amphiphilic behavior in alkaline media.

Pullulan derivative was synthesized by coupling carboxymethylpullulan (degree of substitution DS(0)(in)=0.7) and dimethylaminopropylamine (DMAPA), activated by a hydrosoluble carbodiimide N(')-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDAC). FTIR and (13)C and (1)H NMR spectroscopic analyses have evidenced that the polysaccharide has been successfully modified. (1)H NMR, nitrogen analysis, and conductimetric measurements allow determination of the degree of substitution in both carboxylic acid and amine functions. We have found that both functions present a similar DS of 0.35, which is characteristic of an ampholytic polymer with possible zwitterionic-type properties. Solution properties have been studied by flow field flow fractionation (F4) coupled on-line with multiangle laser light scattering (MALLS) and quasi elastic light scattering (QELS), surface tension, and viscosity measurements. The behavior has been found largely pH dependent and an amphiphilic behavior has been evidenced in alkaline media.

Aggregation of amphiphilic pullulan derivatives evidenced by on-line flow field flow fractionation/multi-angle laser light scattering.

Size-exclusion chromatography (SEC) is a useful steric separation technique for the analysis of water-soluble polysaccharides in aqueous solution. However, in the case of amphiphilic derivatives, the usefulness is limited because of interactions between hydrophobic segments and the stationary phase. Alkyl-bearing pullulans differing from the extent and the length of alkyl groups were characterized using flow-field flow fractionation with on-line coupling multi-angle laser light scattering (F4/MALLS). Comparison of SEC and F4 is presented and the interest of F4 in the field of amphiphilic derivatives is demonstrated.