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C Vauthier

Publications and source records attributed to C Vauthier.

15 recordsLinked to original sources
PubMed2006

Tuning of shell and core characteristics of chitosan-decorated acrylic nanoparticles.

The aim of the work was to develop a new family of chitosan-coated acrylic nanoparticles to increase the specificity of absorption of drugs associated given by the mucosal route. To achieve this goal, techniques of radical and anionic emulsion polymerisation of isobutylcyanoacrylate (IBCA) were used. Changes in the shell composition were made by using chitosan of different molecular weight and thiolated chitosan to modify the particle surface properties in order to vary the mucosae-nanoparticle interactions. The core was also modified by the inclusion of methyl methacrylate (MMA) as second monomer potentially able to improve the control of drug release. Finally, the labelling of nanoparticles core with a fluorophore, methacryloxyethyl thiocarbamoyl rhodamine B (Polyfluor), was successfully achieved, necessary for the in vitro and in vivo evaluation of the systems created. Results showed that nanoparticle size varied from 200 to 500 nm, depending on the molecular weight of chitosan used. Positive surface charge values were obtained in all cases. In addition, evidences of the presence of thiol groups were obtained (0.03-0.16 x 10(-3)micromol/cm(2) of nanoparticle).

Bucrylate↗
PubMed2004

A new generation of polymer nanoparticles for drug delivery.

One of the main interests of using polymer nanoparticles as drug carrier systems is to control the delivery of the drugs including their biodistribution. During the last decade, it was clearly demonstrated that surface properties of nanoparticles were the key factor which determined the in vivo fate of such a carrier. Thus, the purpose of this work was to develop a new method which allows the easy fabrication of nanoparticles with versatile surface properties using polysaccharides. This preparation was based on the use of a redox radical polymerization reaction applied for the first time to the emulsion polymerization of alkylcyanoacrylates in aqueous continuous media. The dispersion of nanoparticles was very stable. The nanoparticle surfaces were coated with polysaccharides and their characteristics can be modulated by the type and the molecular weight of the polysaccharides used during the synthesis. Interestingly the biological properties of the polysaccharide immobilized on the nanoparticle surface can be preserved opening very interesting perspectives for such nanoparticles. This method also offers a new strategy for the design of modular biomimetic nanoparticles as drug carrier systems with multiple functions. One of the applications considered in this work was to use these nanoparticles coupled with haemoglobin as an oxygen carrier.

Complement System Proteins↗
PubMed2003

Drug delivery to resistant tumors: the potential of poly(alkyl cyanoacrylate) nanoparticles.

Simultaneous cellular resistance to multiple lipophilic drugs represents a major problem in cancer chemotherapy. This drug resistance may appear clinically either as a lack of tumor size reduction or as the occurrence of clinical relapse after an initial positive response to antitumor treatment. The resistance mechanism can have different origins either directly linked to specific mechanisms developed by the tumor tissue or connected to the more general problem of distribution of a drug towards its targeted tissue. The purpose of this paper is to summarize the results of the use of poly(alkyl cyanoacrylate) nanoparticles to overcome multidrug resistance (MDR) phenomena at both the cellular and the non-cellular level.

Animals↗
PubMed2002

Absorption and efficiency of insulin after oral administration of insulin-loaded nanocapsules in diabetic rats.

Poly(isobutylcyanoacrylate) nanocapsules have been shown to decrease the blood glucose level after oral administration to streptozotocin-induced diabetic fasted rats after 2 days [Diabetes 37 (1988) 246]. Yet, the absorption of insulin in the blood of rats has not been characterised. The aim of this work was to evaluate the biological activity of insulin given orally as nanocapsules. Humalog-loaded nanocapsules (50 IU/kg) were administered by gavage to streptozotocin-induced diabetic rats. Thirty minutes to 1 h after oral administration, significant levels of human insulin were detected in rat plasma. However, the concentrations were very heterogenous from one rat to another and no decrease of glycemia could be observed. In addition, parenteral injection of insulin in solution showed that high levels of the protein are necessary to decrease blood glucose concentration in diabetic rats. These concentrations were not reached after oral administration. The same dose of insulin decreased glycemia by 50% in normal rats and by only 25% in diabetics. This suggested that an insulino-resistance was developed by streptozotocin-induced diabetic rats.

Animals↗
PubMed1999

Study of the mechanism of insulin encapsulation in poly(isobutylcyanoacrylate) nanocapsules obtained by interfacial polymerization.

In previous studies, insulin-loaded poly(alkylcyanoacrylate) nanocapsules were found to reduce the blood glucose level after oral administration to diabetic rats and dogs. The reduction of the glycemia induced by the nanocapsules was the same regardless of the insulin doses administered, but the effect appeared only after a delay of a few days. The purpose of this study was to investigate the mechanism of insulin encapsulation and the type of interactions that may exist between the polymer forming the nanocapsule wall and the insulin. The results of this study showed, based on the interfacial polymerization of isobutylcyanoacrylate, that the insulin molecule is not chemically modified during the nanoencapsulation process. In addition, no interaction between the poly(isobutylcyanoacrylate) and the insulin could be observed. The observed high encapsulation efficiency of intact insulin may be explained by the fact that the ethanol used in the preparation of the nanocapsules is responsible for the initiation of the interfacial polymerization of isobutylcyanoacrylate instead of the insulin. The zeta potential measurements suggest that insulin is located within the core of the nanocapsules. Thus the biological activity of the nanoencapsulated peptide and the high efficiency of insulin encapsulation achieved with this nanoencapsulation process cannot be explained by a specific interaction of the insulin with the polymer forming the nanocapsule's wall. It may be due, however, to the fact that the encapsulated insulin molecule is chemically intact and located within the oily core of the nanocapsules.

Animals↗
PubMed1999

Physico-chemical characterization of insulin-loaded poly(isobutylcyanoacrylate) nanocapsules obtained by interfacial polymerization.

Insulin could be encapsulated very efficiently in oily containing poly(isobutylcyanoacrylate) nanocapsules obtained by interfacial polymerization. In addition, these nanocapsules showed unexpected biological activity after intragastric administration. The hypoglycemic effect was characterized by a lag time period of 2 days and a prolonged effect over a period of 20 days. To explain, the high encapsulation rate of insulin achieved in these nanocapsules and the biological effect, this work was focused on the characterization of the nanocapsules and on the study of the mechanism of nanocapsule formation. Results showed that insulin was found unmodified during the nanoencapsulation process. This was due to the large amount of ethanol used in the preparation of the nanocapsules that initiated the polymerization of isobutylcyanoacrylate preserving the peptide from a reaction with the monomer. Results also showed that insulin was located inside the core of the nanocapsules and not simply adsorbed onto their surface.

Bucrylate↗
PubMed1999

Spongelike alginate nanoparticles as a new potential system for the delivery of antisense oligonucleotides.

The aim of this study was to design a new antisense oligonucleotide (ON) carrier system based on alginate nanoparticles and to investigate its ability to protect ON from degradation in the presence of serum. Pharmacokinetics and tissue distribution of ON-loaded nanoparticles have been determined after intravenous administration. An original and dynamic process for ON loading into polymeric nanoparticles has been applied. It is based on the diffusion of ON or ON/polylysine complex into the nanoparticle or the alginate gel, respectively. Indeed, the single coincubation of ON with nanoparticles led, within a few days, to an extremely efficient association. The diffusion kinetic of ON was shown to be dependent on several parameters, incubation temperature, ON concentration, presence or absence of polylysine, polylysine molecular weight, and nanoparticle preparation procedure. This new alginate-based system was found to be able to protect [33P]-radiolabeled ON from degradation in bovine serum medium and to modify their biodistribution, as an important accumulation of radioactivity was observed in the lungs, in the liver, and in the spleen after intravenous administration into mice. ON may be associated efficiently with calcium alginate in a colloidal state. Such nanosponges are promising carriers for specific delivery of ON to lungs, liver, and spleen.

Alginates↗
PubMed1998

Biodegradable polyalkylcyanoacrylate nanoparticles for the delivery of oligonucleotides.

Antisense oligonucleotides with base sequences complementary to a specific RNA can, after binding to intracellular mRNA, selectively modulate the expression of a gene. However, these molecules are poorly stable in biological fluids and are characterized by a low intracellular penetration. In view of using oligonucleotides as active molecules, the development of polymeric particulate carriers was considered. Oligonucleotides were associated with biodegradable polyalkylcyanoacrylate nanoparticles through the formation of ion pairs between the negatively charged oligonucleotides and hydrophobic cations. Oligonucleotides bound to these nanoparticles were found to be protected from nuclease attack in cell culture media and their cellular uptake was increased as the result of the capture of nanoparticles by an endocytotic/phagocytotic pathway. The in vivo pharmacokinetic profile of oligonucleotides free or associated with nanoparticles has been investigated after intravenous administration to mice and the stability of these molecules has been evaluated by original methodology based on the use of polyacrylamide gel electrophoresis (PAGE) followed by multichannel radioactivity counting. Stability in vivo in the plasma and in the liver was shown to be improved when the oligonucleotides were adsorbed onto the nanoparticles. These results obtained both in vitro and in vivo open exciting perspectives for the specific delivery of oligonucleotides to the liver, thus considering this approach for the treatment of liver diseases (e.g. liver metastasis or hepatitis).

Animals↗
PubMed1998

Pegylated nanoparticles from a novel methoxypolyethylene glycol cyanoacrylate-hexadecyl cyanoacrylate amphiphilic copolymer.

PURPOSE: The aim of this work was to develop PEGylated poly(alkylcyanoacrylate) nanoparticles from a novel methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate copolymer. METHODS: PEGylated and non-PEGylated nanoparticles were formed by nanoprecipitation or by emulsion/solvent evaporation. Nanoparticles size, zeta potential and surface hydrophobicity were investigated. Surface chemical composition was determined by X-ray photoelectron spectroscopy. Nanoparticle morphology was investigated by transmission electron microscopy after freeze-fracture. Nanoparticles cytotoxicity was assayed in vitro, onto mouse peritoneal macrophages. Cell viability was determined through cell mitochondrial activity, by a tetrazolium-based colorimetric method (MTT test). Finally, the degradation of PEGylated and non-PEGylated poly(hexadecyl cyanoacrylate) nanoparticles was followed spectrophotometrically during incubation of nanoparticles in fetal calf serum. RESULTS: Monodisperse nanoparticles with a mean diameter ranging between 100 and 200 nm were obtained using nanoprecipitation or emulsion/solvent evaporation as preparation procedures. A complete physico-chemical characterization, including surface chemical analysis, allowed to confirm the formation of PEG-coated nanoparticles. The PEGylation of the cyanoacrylate polymer showed reduced cytotoxicity towards mouse peritoneal macrophages. Furthermore, the presence of the PEG segment increased the degradability of the poly(hexadecyl cyanoacrylate) polymer in presence of calf serum. CONCLUSIONS: We succeeded to prepare PEGylated nanoparticles from a novel poly(methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) by two different techniques. Physico-chemical characterization showed the formation of a PEG coating layer. Low cytotoxicity and enhanced degradation were also shown.

Animals↗
PubMed1997

Development of sterically stabilized poly(isobutyl 2-cyanoacrylate) nanoparticles by chemical coupling of poly(ethylene glycol).

To develop rapidly biodegradable "stealth" nanoparticles, a physicochemical investigation was done on the formation of PEG-coated poly(isobutyl 2-cyanoacrylate) (PIBCA) nanoparticles. In particular, this study focused on the effect of polymerization conditions on particle size and surface properties, such as charge and hydrophilicity. Among the parameters involved, the pH of the polymerization medium was found to be a key to control the preparation of PEG-coated nanoparticles. Currently, poly(alkylcyanoacrylate) (PACA) nanoparticles are prepared in H2O at pH 2.5, the most appropriate for producing nanoparticles with a mean diameter of 200 nm and an unimodal size distribution. The presence of PEG in the polymerization medium was shown to affect particles formation: only a pH value < 1.5 led to the formation of colloidal nanoparticles, and slight pH variations dramatically affected particle size and PEG association. Polymer chemistry investigations and chemical determination of PEG strongly suggest that PEG associated with nanoparticles was well copolymerized with PIBCA.

Biocompatible Materials↗
PubMed1997

Complement consumption by poly(ethylene glycol) in different conformations chemically coupled to poly(isobutyl 2-cyanoacrylate) nanoparticles.

There is an increasing interest to develop injectable drug polymeric carriers not recognizable by the body as foreign particles and eliminated very quickly from the bloodstream. A polyethylene glycol (PEG)-coating onto injectable particles showed to reduce either protein adsorption and complement consumption, as a function of the PEG density. In this work we compared the complement rejecting ability of PEG in different conformations coupled to polyisobutylcyanoacrylate (PIBCA) nanoparticles, through the analysis of the residual hemolytic capacity of the human serum after contact with the particles. Nanoparticles were formed by chemical coupling of PEG during emulsion/polymerization of isobutylcyanoacrylate (IBCA). Nanoparticles characterization included an investigation of their surface properties, such as hydrophilicity and conformational mobility of the PEG chains grafted on the nanoparticles surface, and PEG total content. The polymerization kinetics of IBCA in presence of PEG or MePEG were also studied. Complement consumption was observed to be very sensitive to the number of particles in contact with human serum, as well as to the PEG conformation, suggesting PEG configuration could affect the particle exposed surface.

Complement System Proteins↗
PubMed1996

Development of a quantitative polyacrylamide gel electrophoresis analysis using a multichannel radioactivity counter for the evaluation of oligonucleotide-bound drug carrier.

A quantitative polyacrylamide gel electrophoresis (PAGE) analysis using a multichannel radioactivity counter was designed for the evaluation of 33P-labeled antisense oligonucleotide associated with polymeric drug carrier (nanoparticles). The proposed analytical method was first validated. The criteria of specificity, linearity, reliability, detection and quantification limits, and resolution power were determined. Results were compared to those obtained using liquid scintillation counting of crude samples or after solubilization of gel slices. The proposed method gave a better linearity and reliability than liquid scintillation counting of solubilized gel slices. In comparison with the liquid scintillation counting of crude samples, the method presented the advantage of being able to directly separate oligonucleotides differing by only one nucleotide in length. This method was applied for the separation of free oligonucleotides and oligonucleotides bound onto nanoparticles, allowing quantification of the amount of free and bound oligonucleotides without any further separation steps. Thus, because it is easy and rapid, the quantitative PAGE analysis using a multichannel radioactivity counter offers interesting possibilities for the characterization of oligonucleotide nanoparticles.

Cyanoacrylates↗
PubMed1994

Capillary electrophoresis monitoring of the competitive adsorption of albumin onto the orosomucoid-coated polyisobutylcyanoacrylate nanoparticles.

The simultaneous and rapid quantitation of a glycoprotein, human orosomucoid, and a protein, human serum albumin (HSA), by micellar electrokinetic capillary electrophoresis was developed and optimized (pH and sodium dodecyl sulfate concentration) in order to study the competitive adsorption of HSA onto orosomucoid-coated nanoparticles of polyisobutylcyanoacrylate. This method provided satisfactory repeatability and the response was linear for concentrations of orosomucoid and HSA ranging from 0.025 to 0.500 mg/mL (r > 0.994 for both proteins). To study the competitive adsorption of HSA, the amounts of free orosomucoid and free HSA were determined in the supernatant obtained after centrifugation of the orosomucoid-coated nanoparticle suspension incubated with HSA. Furthermore, the quantities of both orosomucoid and HSA absorbed onto nanoparticles were also determined after desorption of these molecules from the nanoparticle surface, using sodium dodecyl sulfate. No analytical interference was observed with this surfactant. The results showed that HSA did not at all absorb onto the orosomucoid-coated nanoparticles and, thus, that this protein did not displace the layer of absorbed orosomucoid from the nanoparticle surface.

Adsorption↗
PubMed1993

Development of a new drug carrier made from alginate.

A new approach for the preparation of nanoparticles is presented. The method is based on control of the gelification phenomenon of alginate by calcium ions, and it leads to small particles of a wide range of very well-defined sizes (250-850 nm) depending on the alignate concentration. The particles are formed in a sodium alginate solution by addition of calcium chloride and then poly-L-lysine. The concentrations of sodium alginate and of calcium chloride were lower than those required for gel formation and corresponded to the formation of a pregel state. The size of the particles formed is greatly dependent on the order of addition of calcium and poly-L-lysine to the sodium alginate solution. This phenomenon can be attributed to the difference in the nature of the interactions between calcium and alginate and between poly-L-lysine and alginate. Furthermore, the data indicate that the formation of the particles probably occurs during the addition of the first component to the sodium alginate solution. Evaluation of the drug-loading capacity was done with doxorubicin as a drug model. The results indicate that alginate nanoparticles are interesting carriers because the drug-loading capacity could be > 50 mg of doxorubicin per 100 mg of alginate.

Alginates↗