Edith Dellacherie

Calcium-alginate beads coated with polycationic polymers: Comparison of chitosan and DEAE-dextran

Abstract The retention capacity of alginate beads coated by two polycationic polymers, chitosan or diethylaminoethyl-dextran (DEAE-dextran) was studied. When beads were stored in water or in a 0·9% NaCl solution, the chitosan coating was stable for more than 5 months or less than 2 months, respectively. The greater the concentration of the polycationic polysaccharides in the formation solution of the beads, the lower the haemoglobin release. Haemoglobin release depended on the pH conditions of bead formation. With chitosan, the lowest release was observed at pH 5·4 (4·4% of released haemoglobin) and at pH 2 (1·5%), respectively, during bead formation and storage. With DEAE-dextran the lowest release was observed at pH 4 (10%).

Amphiphilic derivatives of sodium alginate and hyaluronate: Synthesis and physico-chemical properties of aqueous dilute solutions

This paper reports on the synthesis and the physico-chemical characterisation of various amphiphilic derivatives of two natural polysaccharides, sodium alginate and sodium hyaluronate, in which a rather small proportion of the carboxylic groups (≤10% mol) was esterified by long alkyl chains (C12H25 or C18H37). The derivatives thus prepared were characterised by gas chromatography, 1H and 13C n.m.r. spectroscopy and size exclusion chromatography coupled to a multi-angle laser light scattering detection. The tendency of these water-soluble compounds to hydrophobic association in aqueous solutions was evidenced firstly in dilute regime using capillary viscometry as well as fluorescence spectroscopy in the presence of a molecular probe, 1,1-dicyano-(4′-N,N-dimethylaminophenyl)-1,3-butadiene.

Surface modification of poly(lactic acid) nanospheres using hydrophobically modified dextrans as stabilizers in an o/w emulsion/evaporation technique

Sterically stabilized biocompatible poly(lactic acid) (PLA) nanospheres were prepared by an o/w emulsion/evaporation technique, using hydrophobically modified dextrans (DexP) as the emulsion stabilizer. Photon correlation spectroscopy, zetametry, and differential scanning calorimetry studies corroborated that interfacial adhesion between immiscible dextran and PLA chains was achieved by compatibilization of polymer segments via hydrophobic groups grafted onto dextran and thus leading to the formation of entanglements between the hydrophobic dextran parts and the PLA matrix. The presence of dextran exposed at the particle surface was confirmed by X-ray photoelectron spectroscopy and by the fact that the suspensions showed an increased stability in concentrated NaCl solutions and a reduction of bovine serum albumin adsorption compared to uncoated PLA nanoparticles. A comparison of the characteristics of PLA nanospheres DexP-coated via the emulsion procedure (NS(em)) with those of PLA particles coated by DexP adsorption (NS(ad)) suggests that the conformation of the polymer in the superficial layers may be different. However, both DexP layers behave similarly in terms of stability and protein adsorption.

CALCIUM ALGINATE BEADS COATED WITH CHITOSAN : EFFECT OF THE STRUCTURE OF ENCAPSULATED MATERIALS ON THEIR RELEASE

Bovine serum albumin, human haemoglobin and dextran (with different molecular weights) were encapsulated in calcium alginate beads coated with chitosan. Their release from these modified alginate beads was studied to determine what parameters related to the encapsulated materials govern their release during bead formation and storage. By comparing release of albumin (BSA) and haemoglobin (Hb) that have about the same molecular weight (67000 for BSA and 64500 for Hb), it was found that pH played an important role during both bead formation and storage. pH influences the degree of ionisation of proteins and thus the interactions between proteins and alginate; it also has an influence on the Ca2+-alginate and alginate-chitosan interactions. With neutral molecules such as dextran, release is directly connected to the chain molecular weights, although the flexibility of the encapsulated molecules favours their diffusion through the bead alginate-Ca2+ core and through the polyelectrolyte chitosan-alginate membrane.

Influence of polymeric surfactants on the properties of drug-loaded PLA nanospheres

Abstract Different dextran derivatives containing various grafted hydrophobic groups (phenoxy, P; hexyl, C6 or decyl, C10) were synthesized and their applicability as emulsion stabilizers in the preparation of poly(lactic acid) (PLA) nanospheres by an o/w emulsion/evaporation technique was investigated. The effect of dextran modification on particle size, surface charge and stability was evaluated. Differential scanning calorimetry (DSC) studies suggested that the mechanism of interfacial adhesion between immiscible dextran and PLA chains depend on the nature of the hydrophobic grafted groups. However, all dextran layers behaved similarly in terms of stability and in preventing protein adsorption. The encapsulation of lidocaine in PLA nanoparticles was not possible when using phenoxy–dextran as an emulsion stabilizer in the preparation of particles. Conversely, particles with drug-loading varying from about 7 to 18% (w/w) were obtained in the presence of alkyl–dextrans. The polysaccharide layer at the surface of PLA particles did not significantly change the in vitro release of lidocaine, compared with that obtained with drug-loaded uncoated PLA nanoparticles. The partition coefficient of lidocaine between PLA and water and the drug diffusion in the matrix were found to control the release pattern of lidocaine from nanoparticles.

Amphiphilic derivatives of sodium alginate and hyaluronate for cartilage repair: Rheological properties

Various amphiphilic derivatives of sodium alginate and hyaluronate were prepared by covalent fixation of long alkyl chains (dodecyl and octadecyl) with various ratios on the polysaccharide backbones via ester functions. In the semidilute regime, aqueous solutions of the resulting compounds exhibited the typical rheological properties of hydrophobically associating polymers: tremendous enhancement of zero shear rate Newtonian viscosity, steep shear-thinning behavior, and formation of physically cross-linked gel-like networks. The influence of the alkyl chain length, its content on the polysaccharide and of the polymer concentration in the solution was well identified. All obtained results are discussed with respect to the schedule of conditions related to materials, which could be used for cartilage repair, such as in synovial fluid viscosupplementation as well as in cartilage replacement. In particular, it is seen that HA-C(12)-5 (hyaluronate substituted with 5% of dodecyl chains) and HA-C(18)-1 (hyaluronate substituted with 1% of octadecyl chains) in a 0.15N NaCl solution at 8 g/L have rheological properties quite similar to those of healthy synovial fluid. On the other hand, the rheological parameters of solutions at 8 g/L in 0.15N NaCl of some of derivatives, such as, for example, AA-C(12)-8 (alginate substituted with 8% of dodecyl chains) or HA-C(18)-2, are well fitted for a use in cartilage repair.

Protein C-loaded monomethoxypoly (ethylene oxide)–poly(lactic acid) nanoparticles

This paper deals with the preparation and characterization of monomethoxypoly(ethylene oxide)-poly(lactic acid) (MPEO-PLA) nanoparticles containing protein C, a plasma inhibitor which regulates the mechanism of blood coagulation. Protein C was entrapped in MPEO-PLA nanoparticles using the double emulsion method. The influence of MPEO-PLA copolymers on the different parameters was evaluated: characteristics of protein C-loaded nanoparticles, in vitro release of the protein, evolution of the particle size with incubation time and MPEO release. The nanoparticle size does not depend on copolymer characteristics (MPEO and/or PLA block molecular weight). On the other hand, the efficiency of protein C entrapment is affected by the copolymer characteristics. The burst effect during the protein C release is increased with the hydrophilic character of the copolymer. Moreover, protein C adsorption on the particle surface during its release may be related to MPEO release. Only 25% of the released protein C is active, which clearly illustrates that it is altered during its encapsulation. The optimization of the experimental parameters which disturbed entrapped protein C activity, i.e. sonication time and organic solvent was investigated and has led to a preservation of protein C activity. Then, to optimize its entrapment efficiency, a blend PLA/MPEO-PLA (25/75) was used to prepare nanoparticles. This blend limited burst effect of protein C and its adsorption. However, protein C is only partially released which implicates further investigation for a potential therapeutic use.

Affinity partitioning of steroid-binding proteins. The use of polyethylene oxide-bound estradiol for purifying Δ5→43-oxosteroid isomerase

The purification of steroid high-affinity binding proteins such as ‘transport’ plasma proteins and intracellular ‘receptors’, encounters severe difficulties. They are rather unstable, and present only in low concentration in most soluble extracts [l] . The high affinity of these proteins for their ligands makes possible their purification by affinity chromatography [2]. However, the results obtained so far have not yet been very satisfactory in most cases, essentially because of contamination by polymer-adsorbed ligand, non specific interactions of the bulk of proteins with the matrix, and unstability of the steroid-binding proteins during the elution from biospecific adsorbants [31. The use of polymer aqueous two-phase systems for the partition of various macromolecules has been thoroughly investigated by Albertson [4] and especially the polyethylene oxide-dextran duplex. The latter system has been used successfully to study steroid-binding plasma proteins [5] and the interactions of steroid receptors with DNA [6]. Unfortunately, for purification purposes, the efficiency of this technique is hampered by its lack of specificity. However, if a ligand with a high affinity for the steroid-binding protein is covalently-bound to one of the polymers of the phase system the partition technique is expected to acquire the specificity it otherwise lacks [7-lo] . Since this polymer can be

Protein encapsulation in biodegradable amphiphilic microspheres

MPOE-PLA microspheres containing bovine serum albumin (BSA) were prepared by the double emulsion method with high encapsulation efficiency ( approximately 93%). Confocal scanning microscopic analysis using MPOE-PLA labelled with 1-pyrenemethanol showed the MPOE coating of the microsphere surface. This coating improves the performance of the release system compared with PLA microspheres; the hydrophilic chains reduce the BSA adsorption onto the microspheres and increase the amount of BSA released in the supernatant. Microsphere analysis using atomic force microscopy showed that the presence of the MPOE chains also leads to surface roughness. Studies of the diffusion of 1% rhodamine aqueous solution into the microspheres by means of confocal microscopy showed a fast diffusion of water through the matrices containing high molecular weight MPOE chains (?10 000 g mol-1) and could explain the fast release of BSA from these microspheres.

Biodegradable nanoparticles made from polylactide-grafted dextran copolymers

Polysaccharide-covered polyester nanoparticles were prepared using the emulsion/solvent evaporation process. The core of the nanoparticles was made either of PLA or of a blend of polylactide and polylactide-grafted dextran copolymer in various proportions. The surface of the nanoparticles was covered by dextran chains via the use of water-soluble polylactide-grafted dextrans as polymeric stabilizers during the emulsification step. The characteristics of the nanoparticles (size, surface coverage, thickness of superficial layer, colloidal stability) were correlated to the structural parameters (length and number of polylactide grafts) of the copolymers as well as to their surface active properties. The complete biodegradability of the nanoparticles was evaluated by considering the rate of hydrolysis of polylactide grafts in phosphate buffer and the rate of enzymatic degradation of dextran backbone by dextranase.