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Biomedical subjects

Caroline Lemarchand

Publications and source records attributed to Caroline Lemarchand.

5 recordsLinked to original sources

Influence of polysaccharide coating on the interactions of nanoparticles with biological systems.

Since dextran (DEX) grafted with poly(epsilon-caprolacton) (PCL) side chains (PCL-DEX) copolymers could form nanoparticles with a well defined core-shell structure, we investigated the ability of the DEX coating to modify the interactions with the biological media. We first studied the influence of the DEX coating on the phagocytosis of the nanoparticles by human TPH-1 and J774 murine macrophage-like cell lines. Then, the activation of the complement system (CH50 measurement) at the surface of the particles and the adsorption of plasma proteins (2D-PAGE) were investigated, too. It was found that the modification of the surface with DEX significantly reduced the cytotoxicity towards J774 macrophages: the IC50 was increased from 10 to 600 microg/ml. However, the DEX coating could activate complement, probably due to a loop-like conformation of DEX similar to that of cross-linked DEX in Sephadex (a strong complement activator). In addition, depending on whether the DEX loops were large or compact, preferential adsorption, apolipoproteins or immunoglobulins, was observed.

Adsorption↗

Physico-chemical characterization of polysaccharide-coated nanoparticles.

A series of amphiphilic copolymers (PCL-DEX) made of poly(epsilon-caprolactone) (PCL) side chains grafted onto a dextran (DEX) backbone, was used to modify the surface of PCL nanoparticles. PCL-DEX nanoparticles were prepared by a technique derived from emulsion-solvent evaporation. The purpose of the present study was to investigate the DEX coating (quantification, conformation, mobility) in order to better understand particle surface-protein interactions. The DEX coating was deeply examined using different complementary methods: zeta potential measurement, specific degradation of the DEX shell by dextranase, energy-filtering transmission electron microscopy coupled to image-spectrum electron energy-loss spectroscopy, electronic paramagnetic resonance, high performance size exclusion chromatography as well as nonspecific bovine serum albumin adsorption. All our data together supported a core-shell structure of the nanoparticles, DEX moieties constituting the external coating. The amount of DEX located on the nanoparticle surface was estimated to 70%. The organisation of the shell including chains density and mobility was found to be dramatically influenced by DEX molar mass. The steric repulsion conferred by the presence of DEX at the surface of the nanoparticles decreased the adsorption of albumin. The nanoparticle-protein interaction was, however, greatly influenced by the polysaccharide conformation onto the surface.

Adsorption↗

Polysaccharide-decorated nanoparticles.

Surface modified colloidal carriers such as nanoparticles are able to modulate the biodistribution of the loaded drug when given intravenously, but also to control the absorption of drugs administered by other routes. This review presents the different strategies to coat the surface of polymeric as well as inorganic nanoparticles with polysaccharides. Various physicochemical and biological methods have been described to demonstrate such surface modification. The medical applications, mainly in imaging cancer, of polysaccharide-coated nanoparticles are presented, including their abilities to increase the blood circulation time and to target specific tumoral tissues. It has been shown that these coatings allow also to improve drug absorption via nasal or ocular pathways, due the mucoadhesive and/or permeability enhancer properties of the polysaccharides. Finally, the ability of polysaccharide-coated nanoparticles to deliver DNA or oligonucleotides will be discussed.

Animals↗

Study of emulsion stabilization by graft copolymers using the optical analyzer Turbiscan.

Oil-in-water nanoemulsions were prepared using a series of synthetic graft copolymers with a backbone of dextran (DEX) and a number of side chains of poly-epsilon-caprolactone (PCL). In this paper, we focus on the o/w emulsion stabilizing abilities of these novel PCL-DEX copolymers, using a recently developed optical analyzer (Turbiscan). The main advantage of Turbiscan is to detect the destabilization phenomena in non-diluted emulsion, much earlier than the naked eye's operator, especially in the case of an opaque and concentrated system. This study shows that PCL-DEX copolymers successfully stabilized ethyl acetate-in-water emulsions, even in the absence of additional surfactants, whereas they were not efficient in stabilizing methylene chloride-in-water emulsions which coalesced fast and irreversibly. The ethyl acetate-in-water emulsion stabilizing ability of PCL-DEX seemed to be related to the localization of their blocks with regard to the oil-water interface.

Acetates↗

Novel polyester-polysaccharide nanoparticles.

PURPOSE: The aim of the present study was to develop a new type of core-shell nanoparticles from a family of novel amphiphilic copolymers, based on dextran (DEX) grafted with poly(epsilon-caprolactone) (PCL) side chains (PCL-DEX). METHODS: A family of PCL-DEX copolymers was synthesized in which both the molecular weight and the proportion by weight of DEX in the copolymer were varied. The nanoparticles were prepared by a technique derived from emulsion-solvent evaporation, during which emulsion stability was investigated using a Turbiscan. The nanoparticle size distribution, density, zeta potential, morphology, and suitability for freeze-drying were determined. RESULTS: Because of their strongly amphiphilic properties, the PCL-DEX copolymers were able to stabilize o/w emulsions without the need of additional surfactants. Nanoparticles with a controlled mean diameter ranging from 100 to 250 nm were successfully prepared. A mechanism of formation of these nanoparticles was proposed. Zeta potential measurements confirmed the presence of a DEX coating. CONCLUSION: A new generation of polysaccharide-decorated nanoparticles has been successfully prepared from a family of PCL-DEX amphiphilic copolymers. They may have potential applications in drug encapsulation and targeting.

Chemistry, Pharmaceutical↗