Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture.

PURPOSE: This work investigated the endocytic pathways taken by poly(isobutylcyanoacrylate) (PIBCA) nanoparticles differing in their surface composition and architecture, assuming that this might determine their efficiency of intracellular drug delivery. METHODS: Nanoparticles (A0, A25, A100, R0, R25 ) were prepared by anionic or redox radical emulsion polymerization using mixtures of dextran and fucoidan (0, 25, 100 % in fucoidan). Cell uptake was evaluated by incubating J774A.1 macrophages with nanoparticles. Endocytic pathways were studied by incubating cells with endocytic pathway inhibitors (chlorpromazine, genistein, cytochalasin D, methyl-ß-cyclodextrin and nocodazole) and nanoparticle uptake was evaluated by flow cytometry and confocal microscopy. RESULTS: The fucoidan-coated PIBCA nanoparticles A25 were internalized 3-fold more efficiently than R25 due to the different architecture of the fucoidan chains presented on the surface. Different fucoidan density and architecture led to different internalization pathway preferred by the cells. Large A100 nanoparticles with surface was covered with fucoidan chains in a loop and train configuration were internalized the most efficiently, 47-fold compared with A0, and 3-fold compared with R0 and R25 through non-endocytic energy-independent pathways and reached the cell cytoplasm. CONCLUSION: Internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. In turn, this influenced the extent of internalization and localization of accumulated nanoparticles within cells. The results are of interest for rationalizing the design of nanoparticles for potential cytoplamic drug delivery by controlling the nature of the nanoparticle surface.

Evaluation of zeta potential of nanomaterials by electrophoretic light scattering: Fast field reversal versus Slow field reversal modes.

Zeta potential of nanomaterials designed to be used in nanomedicine is an important parameter to evaluate as it influences in vivo behaviour hence biological activity, efficacy and safety. As mentioned by the International Organization for Standardization (ISO), electrophoretic light scattering is a relevant method for evaluating zeta potential. The present work aimed to validate a new protocol based on the application of Fast Field Reversal mode and to explore its scope with nanomaterials investigated as nanomedicines. Its scope was then compared with that of an already validated protocol which uses both Fast Field Reversal and Slow Field Reversal modes. The new protocol was validated within the framework of the application of the Smoluchowski approximation. Its performances complied with the ISO standard. The protocol could be applied to evaluate mean zeta potential of soft nanomaterials including polymer-based nanoparticles and liposomes. However, it appeared unsuitable to evaluate zeta potential of dense nanomaterials including rutile titanium dioxide nanoparticles. Compared with the previously validated protocol which only applied to the determination of zeta potential of polymer nanoparticles, this new validated protocol gives access to the determination of zeta potential to a wider range of nanomedicines under conditions complying with quality control assessments.

Characterization of nanomedicines' surface coverage using molecular probes and capillary electrophoresis.

A faithful characterization of nanomedicine (NM) is needed for a better understanding of their in vivo outcomes. Size and surface charge are studied with well-established methods. However, other relevant parameters for the understanding of NM behavior in vivo remain largely inaccessible. For instance, the reactive surface of nanomedicines, which are often grafted with macromolecules to decrease their recognition by the immune system, is excluded from a systematic characterization. Yet, it is known that a subtle modification of NMs' surface characteristics (grafting density, molecular architecture and conformation of macromolecules) is at the root of major changes in the presence of biological components. In this work, a method that investigates the steric hindrance properties of the NMs' surface coverage based on its capacity to exclude or allow adsorption of well-defined proteins was developed based on capillary electrophoresis. A series of proteins with different molecular weights (MW) were used as molecular probes to screen their adsorption behavior on nanoparticles bearing different molecular architectures at their surface. This novel strategy evaluating to some degree a functionality of NMs can bring additional information about their shell property and might allow for a better perception of their behavior in the presence of biological components. The developed method could discriminate nanoparticles with a high surface coverage excluding high MW proteins from nanoparticles with a low surface coverage that allowed high MW proteins to adsorb on their surface. The method has the potential for further standardization and automation for a routine use. It can be applied in quality control of NMs and to investigate interactions between proteins and NM in different situations.

Towards quality assessed characterization of nanomaterial: Transfer of validated protocols for size measurement by dynamic light scattering and evaluation of zeta potential by electrophoretic light scattering.

Quality control analysis of nanomaterials has been identified as a major issue to pursue their development in different industrial fields including nanomedicine. One difficulty is the lack of standardized and validated protocols suitable to achieve their characterization. In a previous work, we have developed standardized protocols for the evaluation of the size and zeta potential of nanomaterials based on methods described in the ISO standard and have performed validation of each one. The present work was aimed to transfer these protocols in three independent receiving laboratories. No official guideline was described in the literature to achieve such a transfer. A comparative study for receiving laboratories equipped with the same instrument as the sending laboratory was designed based on the Code of Federal Regulation edited by the Food and Drug Administration. For the receiving laboratory equipped with an instrument working at a different wavelength, a new validation was designed and applied. Corresponding statistical methods were used for the analysis of the results. A successful transfer of the protocols in all receiving laboratories was achieved. All laboratories recorded consistent results applying in blind the protocol of size measurements on two samples of nanomaterials from which included one reference.

Microemulsion systems containing bioactive natural oils: an overview on the state of the art.

Natural oils are extremely complex mixtures containing compounds of different chemical nature. Some of them have physiological or therapeutic activities that may act either alone or in synergy. Therefore, they are used in the pharmaceutical, agronomic, food, sanitary and cosmetic industries. Today, the interest in bioactive natural oils is growing due to their immense potential to prevent and treat numerous human diseases. Formulation in microemulsions (MEs) containing natural oils appeared suitable to improve pharmaceutical and biopharmaceutical properties of bioactive compound derivatives from these oils. Microemulsion systems are thermodynamically stable, transparent, and are isotropic dispersions consisting of oil and water stabilized by an interfacial film of surfactants, typically in combination with a cosurfactant. They can protect labile compounds from premature degradation, control release, increase solubility and hence enhance the bioavailability of poorly bioavailable compounds. The aim of this work was to review the various advantages of bioactive compounds presented in natural oil loaded ME systems to be used as delivery systems. First, the state of the art of the parameters involved in the ME formation, including the basic concepts of the physicochemical formulation of the ME systems, and the main aspects of production and the energy responsible for their formation were reported. The second section describes the use of ME systems and reviews the recent applications of natural oil-loaded in the ME systems as the bioactive compound in the formulation.

Size of monodispersed nanomaterials evaluated by dynamic light scattering: Protocol validated for measurements of 60 and 203nm diameter nanomaterials is now extended to 100 and 400nm.

In vivo fate of nanomaterials is influenced by the particle size among other parameters. Thus, Health Agencies have identified the size of nanomaterial as an essential physicochemical property to characterize. This parameter can be explored by dynamic light scattering (DLS) that is described in the ISO standard 22412:2008(E) and is one of the methods recognized by Health Agencies. However, no protocol of DLS size measurement has been validated over a large range of size so far. In this work, we propose an extension of validation of a protocol of size measurement by DLS previously validated with certified reference materials (CRM) at 60 and 203nm. The present work reports robustness, precision and trueness of this protocol that were investigated using CRM at 100 and 400nm. The protocol was robust, accurate and consistent with the ISO standard over the whole range of size that were considered. Expanded uncertainties were 4.4 and 3.6% for CRM at 100 and 400nm respectively indicating the reliability of the protocol. The range of application of the protocol previously applied to the size measurement of liposomes and polymer nanoparticles was extended to inorganic nanomaterial including silica nanoparticles.

Design, characterisation, and bioefficiency of insulin-chitosan nanoparticles after stabilisation by freeze-drying or cross-linking.

Insulin delivery by oral route would be ideal, but has no effect, due to the harsh conditions of the gastrointestinal tract. Protection of insulin using encapsulation in self-assembled particles is a promising approach. However, the lack of stability of this kind of particles in biological environments induces a low bioavailability of encapsulated insulin after oral administration. The objective of this work was to evaluate the effect of two stabilisation strategies alone or combined, freeze-drying and cross-linking, on insulin-loaded chitosan NPs, and to determine their bioefficiency in vitro and in vivo. NPs were prepared by complex coacervation between insulin and chitosan, stabilised either by cross linking with sodium tripolyphosphate solution (TPP), by freeze-drying or both treatments. In vitro bioefficiency NP uptake was evaluated by flow cytometry on epithelial models (Caco-2/RevHT29MTX (mucus secreting cells)). In vivo, NPs were injected via catheter in the peritoneum or duodenum on insulinopenic rats. Freeze-drying increased in size and charge (+15% vs control 412 ± 7 nm; + 36 ± 0.3 mV) in comparison with cross linking which decreased NP size (-25%) without impacting the NP charge. When combined the consecutive treatments reduced NPs size and increased charges as compared to standard level. Freeze drying is necessary to prevent the destruction of NP in intestinal environment in comparison with no freeze dryed one where 60% of NP were destroyed after 2h. Additionally freeze drying combined with cross linking treatments improved bioefficiency of NP with uptake in cell increased when mucus is present. Combination of both treatment showed a protection of insulin in vivo, with a reduction of glycemia when NPs were administrated. This work showed that the combination of freeze drying and cross linking treatment is necessary to stabilize (freeze-drying) and increase bioefficiency (cross-linking) of self assembled NP in the delivery of insulin in vitro and in vivo.

siRNA associated with immunonanoparticles directed against cd99 antigen improves gene expression inhibition in vivo in Ewing's sarcoma.

Ewing's sarcoma is a rare, mostly pediatric bone cancer that presents a chromosome abnormality called EWS/Fli-1, responsible for the development of the tumor. In vivo, tumor growth can be inhibited specifically by delivering small interfering RNA (siRNA) associated with nanoparticles. The aim of the work was to design targeted nanoparticles against the cell membrane glycoprotein cd99, which is overexpressed in Ewing's sarcoma cells to improve siRNA delivery to tumor cells. Biotinylated poly(isobutylcyanoacrylate) nanoparticles were conceived as a platform to design targeted nanoparticles with biotinylated ligands and using the biotin-streptavidin coupling method. The targeted nanoparticles were validated in vivo for the targeted delivery of siRNA after systemic administration to mice bearing a tumor model of the Ewing's sarcoma. The expression of the gene responsible of Ewing's sarcoma was inhibited at 78% ± 6% by associating the siRNA with the cd99-targeted nanoparticles compared with an inhibition of only 41% ± 9% achieved with the nontargeted nanoparticles.

Cytotoxicity and cellular uptake of newly synthesized fucoidan-coated nanoparticles.

The aim was to synthesize and characterize fucoidan-coated poly(isobutylcyanoacrylate) nanoparticles. The nanoparticles were prepared by anionic emulsion polymerization (AEP) and by redox radical emulsion polymerization (RREP) of isobutylcyanoacrylate using fucoidan as a new coating material. The nanoparticles were characterized, and their cytotoxicity was evaluated in vitro on J774 macrophage and NIH-3T3 fibroblast cell lines. Cellular uptake of labeled nanoparticles was investigated by confocal fluorescence microscopy. Results showed that both methods were suitable to prepare stable formulations of fucoidan-coated PIBCA nanoparticles. Stable dispersions of nanoparticles were obtained by AEP with up to 100% fucoidan as coating material. By the RREP method, stable suspensions of nanoparticles were obtained with only up to 25% fucoidan in a blend of polysaccharide composed of dextran and fucoidan. The zeta potential of fucoidan-coated nanoparticles was decreased depending on the percentage of fucoidan. It reached the value of -44 mV for nanoparticles prepared by AEP with 100% of fucoidan. Nanoparticles made by AEP appeared more than four times more cytotoxic (IC(50) below 2 µg/mL) on macrophages J774 than nanoparticles made by RREP (IC(50) above 9 µg/mL). In contrast, no significant difference in cytotoxicity was highlighted by incubation of the nanoparticles with a fibroblast cell line. On fibroblasts, both types of nanoparticles showed similar cytotoxicity. Confocal fluorescence microscopy observations revealed that all types of nanoparticles were taken up by both cell lines. The distribution of the fluorescence in the cells varied greatly with the type of nanoparticles.

Cyclodextrin complexed insulin encapsulated hydrogel microparticles: An oral delivery system for insulin.

An oral insulin delivery system based on methyl-ß-cyclodextrin (MCD) complexed insulin encapsulated polymethacrylic acid (PMAA) hydrogel microparticles was evaluated in this investigation. Poly(methacrylic acid)-chitosan-polyethylene glycol (PCP) microparticles were prepared by ionic gelation method. The insulin-MCD (IC) complex prepared was characterized by fluorescence spectroscopic and isothermal titration micro-calorimeteric (ITC) methods. MCD complexed insulin was encapsulated onto PCP microparticles by diffusion filling method. Loading and release properties of the complexed insulin from microparticles were evaluated under in vitro conditions. The effect of MCD complexation on the permeability of insulin was studied using Caco 2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. In vivo experiments were carried on streptozotocin induced diabetic rats to evaluate the efficacy of MCD complexed insulin encapsulated PCP microparticles to deliver insulin by the oral route. IC complex formation was established by fluorescence and ITC investigations. Insulin loading and release properties from the hydrogel matrix was rather unaffected by the MCD complexation. However MCD complexation was effective in enhancing insulin transport across Caco 2 cell monolayers, when applied in combination with the PMAA hydrogel system. Both insulin and MCD complexed insulin encapsulated PCP microparticles were effective in reducing blood glucose level in diabetic animal models. Cyclodextrin complexed insulin encapsulated hydrogel microparticles appear to be an interesting candidate for oral delivery of insulin.

Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.

In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides.

Surface-functionalized polymethacrylic acid based hydrogel microparticles for oral drug delivery.

Aim of the present work was to develop novel thiol-functionalized hydrogel microparticles based on poly(methacrylic acid)-chitosan-poly(ethylene glycol) (PCP) for oral drug delivery applications. PCP microparticles were prepared by a modified ionic gelation process in aqueous medium. Thiol modification of surface carboxylic acid groups of PCP micro particles was carried out by coupling l-cysteine with a water-soluble carbodiimide. Ellman's method was adopted to quantify the sulfhydryl groups, and dynamic light-scattering technique was used to measure the average particle size. Cytotoxicity of the modified particles was evaluated on Caco 2 cells by MTT assay. Effect of thiol modification on permeability of paracellular marker fluorescence dextran (FD4) was evaluated on Caco 2 cell monolayers and freshly excised rat intestinal tissue with an Ussing chamber set-up. Mucoadhesion experiments were carried out by an ex vivo bioadhesion method with excised rat intestinal tissue. The average size of the PCP microparticles was increased after thiol modification. Thiolated microparticles significantly improved the paracellular permeability of FD4 across Caco 2 cell monolayers, with no sign of toxicity. However, the efficacy of thiolated system remained low when permeation experiments were carried out across excised intestinal membrane. This was attributed to the high adhesion of the thiolated particles on the gut mucosa. Nevertheless, it can be concluded that surface thiolation is an interesting strategy to improve paracellular permeability of hydrophilic macromolecules.

Combined hydroxypropyl-beta-cyclodextrin and poly(anhydride) nanoparticles improve the oral permeability of paclitaxel.

The aim of this work was to study the effect of the combination between 2-hydroxypropyl-beta-cyclodextrin (HPCD) and bioadhesive nanoparticles on the encapsulation and intestinal permeability of paclitaxel (PTX). In this context, a solid inclusion complex between PTX and HPCD was prepared by an evaporation method. Then, the complex was incorporated in poly(anhydride) nanoparticles by a solvent displacement method. The resulting nanoparticles, PTX-HPCD NP, displayed a size of about 300 nm and a drug loading of about 170 microg/mg (500-fold higher than in the absence of HPCD). The effect of these nanoparticles on the permeability of intestinal epithelium was investigated using the Ussing chamber technique. The apparent permeability (P(app)) of PTX was found to be 12-fold higher when formulated as PTX-HPCD NP than when formulated as Taxol (control). Furthermore, when interaction between nanoparticles and the mucosa was avoided, the permeability of PTX significantly decreased. In summary, the association between PTX-HPCD and poly(anhydride) nanoparticles would induce a positive effect over the intestinal permeability of paclitaxel, being the bioadhesion a mandatory condition in this phenomena.

Polymer nanocarriers for the delivery of small fragments of nucleic acids: oligonucleotides and siRNA.

The success of the application of new therapeutic methods based on RNA interfering strategies requires the in vivo delivery of active ODN or siRNA down to the intracellular compartment of the target cells. This article aims to review the studies related to the formulation of RNA interfering agents in polymer nanocarriers. It will present the different types of polymer nanocarriers used as well as the biological activity of the resulting ODN and siRNA loaded nanocarriers. As will be explained, the part of the in vitro studies provided useful data about the intracellular delivery of the formulated RNA interfering agents. Investigations performed in vivo have considered animal models of different relevant diseases. Results from these investigations have clearly demonstrated the interest of several polymer nanocarriers tested so far to deliver active RNA interfering effectors in vivo making possible their administration by the intravenous route.

How to concentrate nanoparticles and avoid aggregation?

Most of the methods that are used to produce pharmaceutical suspensions of nanoparticles for drug-targeting yield suspensions having a low content in drug carriers. This can be a dramatic limitation when the volume of suspension that would have to be administered in vivo to reach therapeutic concentrations of the drug is much above the acceptable range. Concentrating the drug-carrier suspension by centrifugation, lyophilization and evaporation is often inapplicable because aggregates are formed. Here we present a simple method that is able to increase the concentration of nanoparticle suspensions without forming aggregates. It consists in a dialysis of the suspensions against a polymer solution. This causes an osmotic stress, which produces a displacement of water from the nanoparticle suspension towards the counter-dialysing solution. Various types of nanoparticle suspensions can be concentrated in near equilibrium conditions, and the result is controlled and reproducible. Concentration factors up to 50 were obtained in a few hours at room temperature. The original characteristics of the nanoparticles were fully preserved in the concentrated dispersion.

Specific permeability modulation of intestinal paracellular pathway by chitosan-poly(isobutylcyanoacrylate) core-shell nanoparticles.

This work is focused on the evaluation of the in vitro permeation modulation of chitosan and thiolated chitosan (chitosan-TBA) coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles as drug carriers for mucosal administration. Core-corona nanoparticles were obtained by radical emulsion polymerisation of isobutylcyanoacrylate (IBCA) with chitosan of different molecular weights and different proportions of chitosan/chitosan-TBA. In this work, the effect of these nanoparticles on the paracellular permeability of intestinal epithelium was investigated using the Ussing chamber technique, by adding nanoparticle suspensions in the mucosal side of rat intestinal mucosa. Results showed that permeation of the tracer [14C]mannitol and the reduction of transepithelial electrical resistance (TEER) in presence of nanoparticles were more pronounced in those formulations prepared with intermediate amounts of thiolated polymer. This effect was explained thanks to the high diffusion capacity of those nanoparticles through the mucus layer that allowed them to reach the tight junctions in higher extent. It was concluded that, although a first contact between nanoparticles and mucus was a mandatory condition for the development of a permeation enhancement effect, the optimal effect depended on the chitosan/chitosan-TBA balance and the conformational structure of the particles shell.

Characterization of chitosan thiolation and application to thiol quantification onto nanoparticle surface.

The objective of the present work was to establish a simple and appropriated method for the quantification of thiol groups standing on the surface of core-shell nanoparticles elaborated with poly(isobutyl cyanoacrylates) and thiolated chitosan. A critical analysis of the widely used Ellman's method for the determination of thiol groups in various compounds was made. The reduced solubility of the thiolated polymer at the optimal pH of the Ellman's assay (pH 8-8.5) made difficult the accessibility of the Ellman's reagent to thiol groups in the cross-linked polymer. Furthermore, the lack of stability of the Ellman's reaction with time lead to the conclusion that the Ellman's method was of limited value to evaluate thiol groups in thiolated polymers like thiolated chitosan. An alternative and very simple thiol quantification method was developed on the bases of the classical iodine titration. The new method allowed the determination of thiol groups in small amount of samples at acidic pH, and the monitoring of the thiol determination kinetic with time. It was successfully applied to the quantification of active thiol groups on the surface of poly(isobutyl cyanoacrylates) nanoparticles coated with thiol chitosan.

In vitro evaluation of calcium binding capacity of chitosan and thiolated chitosan poly(isobutyl cyanoacrylate) core-shell nanoparticles.

The ability of chitosan and its derivatives to bind cations is well known. Chitosan and thiolated chitosan were recently associated with poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles leading to very promising results in terms of bioadhesion and permeation enhancement properties. Taking into account the influence that cations concentration have in the maintenance of both the permeation and the enzymatic barrier of the oral route, the possible cation binding capacity of these colloidal systems might be interesting in the use of these nanocarriers for the oral administration of pharmacologically active peptides. The aim of the present work was to in vitro evaluate the capacity of these colloidal systems to bind calcium, a model cation of physiological interest in the intestinal tract. The presence of chitosan on the nanoparticle surface importantly increased the calcium binding ability, in comparison to non-coated PIBCA nanoparticles. In addition, its presentation in the gel layer surrounding the nanoparticles, also beneficiated its binding capacity, obtaining 2-3 folds higher values when the polymer coated the nanoparticles than when it was in solution. The cross-linked structure observed for thiolated chitosan, due to the formation of inter- and intra-chain disulphide bonds, diminished the accessibility of cation to active sites of the polymer, decreasing the binding capacity of the calcium ion. However, when the amount of free thiol groups on the nanoparticle surface was high enough, the binding behaviour observed was higher than for nanoparticles elaborated with non-modified polymer.

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).

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.