Biomedical subjects

Christine Vauthier

Publications and source records attributed to Christine Vauthier.

18 recordsLinked to original sources

PubMed2006

PEGylation of microspheres for therapeutic embolization: preparation, characterization and biological performance evaluation.

In this study, microspheres designed for embolization, defined as GF2000-Trisacryl MS (GF-MS) and DEAE-Trisacryl MS (DEAE-MS), were originally PEGylated using (3-amino propyl) triethoxy silane as coupling agent. Indomethacin was loaded into both PEGylated and non-PEGylated DEAE-MS, displaying ion-exchange ability, through a batch process with a respective capacity of 1.2 and 0.25 g/g. The morphology of naked and PEGylated MS was evaluated by scanning electron microscopy (SEM). Both micosphere resins surface looked like orange skin, although DEAE-MS showed a slightly rougher surface due to the copolymerization process. PEGylated microspheres have a most likely swelling surface owing to the presence of PEG hydrophilic chains. The mean diameters were of about 66 and 60 microm for GF-MS and DEAE-MS, respectively. Data obtained for PEGylated MS by Fourier Transform Infrared spectroscopy (FTIR) confirmed that microspheres were successfully PEGylated. Finally, complement activation in vitro was performed to evaluate the activating capacity of different microspheres. Both PEGylated GF-MS and DEAE-MS activated the complement system of about 33% less than their corresponding naked microspheres, while loading PEGylated DEAE-MS with indomethacin almost suppressed complement activation. This inhibiting role implies that PEGylation as well as loading the microspheres with anti-inflammatory drug has a compact effect on the interaction of microspheres with blood proteins.

Biocompatible Materials↗

PubMed2006

Development and in vitro evaluation of a thiomer-based nanoparticulate gene delivery system.

Chitosan-thiobutylamidine was developed and evaluated as a novel tool for gene delivery. The conjugate, displaying 299.1+/-11.5 micromol free thiol groups per gram polymer, formed coacervates with pDNA at a mean size of 125 nm and a zeta potential of +9 mV. Thiol groups, being susceptible for oxidation, were immobilised on the polymeric backbone of chitosan in order to introduce the property of extracellular stability and intracellular pDNA release by forming reversible disulfide bonds. The integrity of the new particles was compared to unmodified chitosan under simulated physiological conditions. Within 10h, pDNA was completely released from chitosan-DNA particles while only 12% were released from the thiomer-based particles. At pH 7, the amount of thiol groups significantly (p<0.05) decreased by more than 25% within 6h. In contrast, in a reducing environment as found intracellularly, chitosan-thiobutylamidine-DNA nanoparticles dissociated continuously, liberating approximately 50% of pDNA within 3h. Transfection studies performed in a Caco2 cell culture evinced the highest efficiency for chitosan-thiobutylamidine-DNA nanoparticles in combination with a glycerol shock solution. The combination of improved stability, enhanced pDNA release under reducing conditions, and higher transfection efficiency identifies chitosan-thiobutylamidine as a promising new vector for gene delivery.

Butylamines↗

PubMed2006

Nanoscopic core-shell drug carriers made of amphiphilic triblock and star-diblock copolymers.

The aim of this work was to design injectable nanocarriers for drug delivery based on PCL-PEO amphiphilic block copolymers with linear ABA triblock and 4-armed (BA)(4) star-diblock architectures (A=PEO, B=PCL). The copolymers were obtained by coupling of a monofunctional -COOH end-capped PEO (M(n)=2.0kDa) with linear or 4-armed star-shaped PCL macromers bearing -OH terminal groups and were characterized by (1)H NMR spectroscopy and size exclusion chromatography. DSC and X-ray diffraction experiments showed that separate crystalline phases of PCL and PEO are present in bulk copolymers. Nanoparticles were produced by nanoprecipitation (NP) and by a new melting-sonication procedure (MS) without the use of toxic solvents, and characterized for size, polydispersity, zeta potential and core-shell structure. Nanoparticles were loaded with all-trans-retinoic acid (atRA) as a model drug and their release features assessed. Results demonstrate that both techniques allow the formation of PEO-coated nanoparticles with a hydrodynamic diameter that is larger for nanoparticles prepared by MS. atRA is released from nanoparticles at controlled rates depending on size, loading and, more important, preparation technique, being release rate faster for MS nanoparticles. Some biorelevant properties of the carrier such as complement activation were finally explored to predict their circulation time after intravenous injection. It is demonstrated that nanoparticles prepared by MS do not activate complement and are of great interest for future in vivo applications.

Calorimetry, Differential Scanning↗

PubMed2006

Nanotechnology: intelligent design to treat complex disease.

The purpose of this expert review is to discuss the impact of nanotechnology in the treatment of the major health threats including cancer, infections, metabolic diseases, autoimmune diseases, and inflammations. Indeed, during the past 30 years, the explosive growth of nanotechnology has burst into challenging innovations in pharmacology, the main input being the ability to perform temporal and spatial site-specific delivery. This has led to some marketed compounds through the last decade. Although the introduction of nanotechnology obviously permitted to step over numerous milestones toward the development of the "magic bullet" proposed a century ago by the immunologist Paul Ehrlich, there are, however, unresolved delivery problems to be still addressed. These scientific and technological locks are discussed along this review together with an analysis of the current situation concerning the industrial development.

Animals↗

PubMed2006

Properties of polysaccharides grafted on nanoparticles investigated by EPR.

The in vivo fate of nanoparticles developed as drug delivery systems is influenced by the surface characteristics of the colloidal particles. In the present work, surface characteristics of a series of poly(isobutylcyanoacrylate) nanoparticles prepared by redox radical emulsion polymerization with polysaccharides of different molecular weight and nature were characterized by EPR. To this aim, a spin label was grafted on the polysaccharide chains after synthesis of the nanoparticles. The percentage of label showing fast movements was evaluated from EPR spectra which were analyzed according to the Kivelson theory. The results showed that mobility depended on temperature, type, and molecular weight of the polysaccharides. Differences between nanoparticles appeared with low-molecular-weight polysaccharides, while over a defined molecular weight which depended on the nature of the polysaccharide, the spin label behaved almost the same way in the different types of nanoparticles. Paradoxically, the percentage of fast moving label was the highest when linked to the shortest chitosan, which was the most rigid polysaccharide tested in this study. Thus, it was concluded that the apparent mobility of the polysaccharide evaluated by the EPR method depended on the capacity of the polysaccharide chains to fold making possible hydrophobic interactions between the label and the nanoparticle core. The transition between the unfolded-folded regiment depended on the molecular weight and on the nature of the polysaccharide. Results of this study may be useful to improve the understanding of the nanoparticle interactions with blood proteins and complement which in turn influence the in vivo fate of nanoparticles used as drug delivery systems.

Cyanoacrylates↗

PubMed2006

Complement activation by core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles: influences of surface morphology, length, and type of polysaccharide.

PURPOSE: Biodistribution of intravenously administered nanoparticles depends on opsonization. The aim of this study was the evaluation of complement activation induced by nanoparticles coated with different polysaccharides. Influences of size and configuration of dextran, dextran sulfate, or chitosan bound onto nanoparticles were investigated. METHOD: Core-shell nanoparticles were prepared by redox radical or anionic polymerization of isobutylcyanoacrylate in the presence of polysaccharides. Conversion of C3 into C3b in serum incubated with nanoparticles was evaluated. RESULTS: Cleavage of C3 increased with size of dextran bound in "loops" configuration, whereas it decreased when dextran was bound in "brush." It was explained by an increasing steric repulsive effect of the brush, inducing poor accessibility to OH groups. The same trend was observed for chitosan-coated nanoparticles. Nanoparticles coated with a brush of chitosan activated the complement system lesser than nanoparticles coated with a brush of dextran. This was explained by an improved repelling effect. Dextran-sulfate-coated nanoparticles induced a low cleavage of C3 whereas it strongly enhanced protein adsorption. CONCLUSION: Complement activation was highly sensitive to surface features of the nanoparticles. Type of polysaccharide, configuration on the surface, and accessibility to reactive functions along chains are critical parameters for complement activation.

Chitosan↗

PubMed2006

Elaboration and characterization of thiolated chitosan-coated acrylic nanoparticles.

The aim of the present work was to investigate the use of thiolated chitosan in the development of polysaccharide-coated nanoparticles in order to confer specific functionality to the system. After chemical modification of commercial and hydrolysed chitosan (400,000 and 9400 g/mol respectively), thiolated chitosans were used to elaborate particles in the nano-range. They were characterized in terms of size and surface charge measurement. Both analysis showed nanoparticles of mean hydrodynamic diameter around 200 nm and positive zeta potential values, indicating the presence of the cationic polysaccharide at the nanoparticle surface. Moreover, the Ellman's reaction was used to demonstrate the presence of thiol groups at the particle surface. The observation of nanoparticles by scanning electronic microscopy (SEM) showed spherical nanoparticles for all formulations. This new system, combining both the advantages of thiolated polymers and colloidal particles can be proposed as an original drug carrier system for mucosal delivery of biotechnology products.

Chitosan↗

PubMed2005

Interactions of blood proteins with poly(isobutylcyanoacrylate) nanoparticles decorated with a polysaccharidic brush.

The aim of this work was to examine the in vitro interactions of core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles (NP) with blood proteins. The particles were prepared by initiating the emulsion polymerization of isobutylcyanoacrylate (IBCA) in the presence of dextran 71 or 15 kDa, heparin, a blend of dextran 71 and heparin, or dextran sulphate in aqueous medium at pH 1. The mechanisms of polymerisation were redox radical (Rad) or anionic (An), resulting in differences in the spatial arrangement of the polysaccharide chains at the NP surface, i.e. "loops" and "trains" by anionic polymerization, "brush" by radical polymerization. Surface composition of NPs was determined by X-ray photo-electron spectroscopy (XPS) and surface charge by zeta potential measurements. In the presence of citrated blood plasma, efficacy of the steric repulsive effect of the NP dextran shell towards protein adsorption decreased in the order: Dex71-Rad > Dex15-Rad > Dex71-AnDex15-An. Dextran-coated NPs adsorbed ApoA-I and fibrinogen from plasma. Concerning activation of complement in serum, the effect was sharp: Dex71-Rad was a very low activator whereas Dex15-An, Dex15-Rad and Dex71-An were strong activators. In citrated plasma, the steric repulsive effects of Hep-Rad and Dex-Hep-Rad NPs were similar to Dex71-An, and Dex-Sulph-Rad NPs adsorbed twice more proteins than Hep-Rad. Hep-Rad, Dex-Hep-Rad and Dex-Sulph-Rad NPs adsorbed IgG and fibrinogen. Complement was not activated in serum in the presence of Hep-Rad and Dex-Hep-Rad and a slight adsorption of C3 was noted. C3 was completely adsorbed on Dex-Sulph-Rad. The exquisite sensitivity of blood proteins to differences in the nature and outermost structure of the polysaccharides-coated NPs is highlighted by the present results.

Adsorption↗

PubMed2004

Heparin coated poly(alkylcyanoacrylate) nanoparticles coupled to hemoglobin: a new oxygen carrier.

A new generation of drug delivery systems based on heparin-poly(isobutylcyanoacrylate) copolymers has been developed to carry hemoglobin. These copolymers spontaneously form, in water, nanoparticles with a ciliated surface of heparin. These nanoparticles maintain the heparin antithrombotic properties and inhibit complement activation. One ml of nanoparticle suspension can be loaded with up to 2.1mg of hemoglobin, which preserves its ligand binding capacity. This work constitutes the first demonstration of hemoglobin loaded on nanoparticle surface, rather than being encapsulated. With a size of 100 nm, these drug delivery systems make suitable tools in the treatment of thrombosis oxygen deprived pathologies.

Adult↗

PubMed2004

Insulin-loaded W/O/W multiple emulsions: comparison of the performances of systems prepared with medium-chain-triglycerides and fish oil.

Insulin-loaded W/O/W multiple emulsions (ME) composed of medium-chain triglycerides have been shown to decrease the blood glucose level after oral administration to diabetic rats. Fish oil (very long-chain triglycerides) could be an alternative to medium-chain triglycerides because its chronic consumption has beneficial therapeutic effects. The aim of this work was twofold: to obtain stable fish oil containing ME, based on a formulation optimized in a previous work with low medium-chain triglycerides content, and to compare their characteristics to those of ME composed of medium-chain triglycerides. Due to the higher viscosity and surface tension of fish oil compared to medium-chain triglycerides, preparation of ME appeared difficult to achieve. However, a stable unloaded-ME with low fish oil content was formed, by adapting the emulsification process. The characteristics of unloaded fish oil ME were almost similar to those of medium-chain triglycerides ME. In contrast to medium-chain triglycerides ME, the introduction of insulin did not improve the elasticity and consequently the characteristics and stability of fish oil ME. Nevertheless, the insulin-loaded fish oil containing ME was shown to be stable for 6 weeks at 4 degrees C.

Emulsions↗

PubMed2004

Evidence for restrictive parameters in formulation of insulin-loaded nanocapsules.

Poly(isobutylcyanoacrylate) nanocapsules with an oily core were originally proposed for lipophilic drug encapsulation [Int. J. Pharm. 28 (1986) 125] but insulin, a hydrosoluble protein, has also been successfully encapsulated by Damgé et al. [Diabetes 37 (1988) 246]. The aim of this work was to understand if several parameters were restrictive for the encapsulation of insulin into the oily core of the nanocapsules prepared by interfacial polymerization. The encapsulation efficiency of insulin was not affected by the type of insulin since the peptides adopted the same association state after their addition to the organic phase. Formulation parameters mainly affected the size of the nanocapsules obtained but did not influence the insulin encapsulation efficiency. In contrast, the order of introduction of insulin and of the monomer in the organic phase was shown to control the formation and the characteristics of the nanocapsules. The key parameters, which were found to clearly influence the encapsulation efficiency of insulin, were the pH of the aqueous insulin solution and the origin of the monomer. Both of these parameters can affect the rate of the interfacial polymerization. Consequently, the ability of insulin to be entrapped into the oil containing nanocapsules appeared to be governed more by the rate of the monomer polymerization.

Animals↗

PubMed2003

Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications.

This review considers the use of poly(alkylcyanoacrylates) (PACAs) as biomedical materials. We first present the different aspects of the polymerization of alkylcyanoacrylate monomers and briefly discuss their applications as skin adhesives, surgical glues and embolitic materials. An extensive review of the developments and applications of PACAs as nanoparticles for the delivery of drugs is then given. The methods of preparation of the nanoparticles are presented and considerations concerning the degradation, in vivo distribution, toxicity and cytotoxicity of the nanoparticles are discussed. The different therapeutic applications are presented according to the route of administration of the nanoparticles and include the most recent developments in the field.

Absorbable Implants↗

PubMed2003

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↗

PubMed2003

Visualization of insulin-loaded nanocapsules: in vitro and in vivo studies after oral administration to rats.

PURPOSE: Biodegradable poly(isobutylcyanoacrylate) nanocapsules have been recognized as a promising carrier for oral administration of peptides and proteins. In the present study, we investigate the fate of insulin-loaded nanocapsules by fluorescence and transmission electron microscopy (TEM) after intragastric force-feeding to rats. METHODS: Insulin-, Texas-red-labeled insulin, or gold-labeled insulin-loaded nanocapsules were first characterized. Rats received a single dose of nanocapsules (diameter 60-300 nm, 57 IU insulin/kg) by intragastric force-feeding. After 90 min, ileum was isolated and prepared for fluorescence and transmission electron microscopy. RESULTS: Nanocapsules were observed on both sides of the gut epithelium and in blood capillaries. In M-cell-free epithelium, apparently intact nanocapsules could be seen in the underlying tissue, suggesting they could cross the epithelium and carry the encapsulated peptide. In M-cell-containing epithelium, nanocapsules appeared degraded in the vicinity of macrophages. It is noteworthy that intestinal absorption of nanocapsules was observed without artifacts forcing the nanocapsules to stay in the gut. CONCLUSIONS: Based on TEM observations, this study shows the intestinal absorption of biodegradable nanocapsules leading to the transport of insulin across the epithelium mucosa. The fate of the nanocapsules appeared different depending on the presence or the absence of M cells in the intestinal epithelium.

Administration, Oral↗

PubMed2003

Novel polysaccharide-decorated poly(isobutyl cyanoacrylate) nanoparticles.

PURPOSE: The aim of this work was to synthesize new surface-modified nanoparticles using a radical emulsion polymerization of an alkyl cyanoacrylate. METHODS: Isobutyl cyanoacrylate was polymerized in nitric acid 0.2 M containing a polysaccharide (0.1375 g) and cerium (8 x 10(-2) M). After 1 h, the pH was adjusted to 7.0, and the nanoparticles were purified by dialysis. Nanoparticle characterization included scanning electron microscopy, quasi-elastic light scattering, zeta potential determination, measurements of the complement activation induced by different polysaccharide-coated nanoparticles and of the antithrombic activity of heparin. RESULTS: Dispersions of spherical particles were obtained using various polysaccharides. The particle diameter varied from 90 nm to several micrometers, and the zeta potential depended on the molecular weight and the nature and charge of the polysaccharide. Surface analysis performed by ESCA confirmed the presence of polysaccharides at the nanoparticle surface. The nanoparticles were very stable, and the biologic activity of the polysaccharide was preserved. Complement activation was influenced by the polysaccharide characteristics. CONCLUSIONS: A new method based on radical emulsion polymerization of isobutyl cyanoacrylate initiated by polysaccharides and cerium was developed to prepare nanoparticles. It leads, in a single step, to nanoparticles with surface properties defined by the polysaccharide. This method is a new concept for the development of biomimetic drug carriers with multiple functions.

Cyanoacrylates↗

PubMed2002

Nanocapsule technology: a review.

Nanocapsules are submicroscopic colloidal drug carrier systems composed of an oily or an aqueous core surrounded by a thin polymer membrane. Two technologies can be used to obtain such nanocapsules: the interfacial polymerization of a monomer or the interfacial nanodeposition of a preformed polymer. This article is an extended review of these nanocapsule technologies and their applications for the treatment of various diseases (including cancer and infections).

Animals↗

PubMedDate not supplied

Bioadhesive properties of poly(alkylcyanoacrylate) nanoparticles coated with polysaccharide.

Development of bioadhesive nanoparticles is of great interest to improve drug absorption through the intestinal barrier. Various Polysaccharide-coated poly(alkylcyanoacrylate) nanoparticles were prepared. The bioadhesive properties of the nanoparticles coated with dextran or chitosan in end-on or side-on conformation were evaluated with an ex-vivo adsorption experiment on rat intestine. Results show that diffusion of nanoparticles in mucus layer was governed by the nanoparticle diameter and isotherms of adsorption were influenced by the nature of polysaccharide used. High amount of nanoparticles coated with chitosan can be entrapped in the mucus layer even at low nanoparticle concentration in suspension. When nanoparticle concentration increased, a pseudo-plateau was reached. In the case of dextran-coated nanoparticles, linear increase of adsorption was observed and no saturation phenomenon was highlighted over the range of nanoparticle concentration used in this study. These results suggested that interactions involved in bioadhesion mechanism depended on the nature of polysaccharide. Electrostatic interactions are enhanced between chitosan-coated nanoparticles and glycoproteins of mucus leading to a saturated adsorption phenomenon whereas dextran-coated nanoparticles interacted by non-electrostatic interactions with mucus resulting in a non-saturated phenomenon. Polysaccharides grafted at the nanoparticle surface in the brush conformation appeared more favorable to promote interactions of nanoparticles with glycoproteins of mucus in comparison with the more compact loop conformation of polysaccharide chains.

Adhesiveness↗

PubMedDate not supplied

Development of a novel vaccine delivery system based on Gantrez nanoparticles.

The adjuvant capacity of a novel vaccine vector "Gantrez-nanoparticles" (NP) towards coated or encapsulated ovalbumin (OVA) was investigated. OVA nanoparticles were prepared by a solvent displacement method previously described. The protein was incorporated during the manufacturing process (OVA-encapsulated nanoparticles) or after the preparation (OVA-coated nanoparticles). The mean size of the different nanoparticle formulations was lower than 300 nm, and the OVA content ranged approximately from 67 microg/mg nanoparticles (for OVA-coated nanoparticles) to 30 microg/mg nanoparticles (for OVA-encapsulated nanoparticles). All the OVA-NP formulations were capable of amplifying the antibodies titres (IgG1 and IgG2a) in mice after a single subcutaneous inoculation with respect free OVA or OVA adsorbed to Alum. Furthermore, the elicited response was, for some formulations, predominantly Th1 subtype. Thus, the formulation that contained mainly the antigen inside, and with a low concentration of cross-linking agent, displayed the best potential to induce a Th1 response after 35 days post-immunisation. These results are highly suggestive for the use of Gantrez nanoparticles as an efficient antigen delivery system, especially when a long lasting Th1 cytokine response is required.

Adjuvants, Immunologic↗