Frank Boury

Synthesis of hollow vaterite CaCO3 microspheres in supercritical carbon dioxide medium

We here describe a rapid method for synthesizing hollow core, porous crystalline calcium carbonate microspheres composed of vaterite using supercritical carbon dioxide in aqueous media, without surfactants. We show that the reaction in alkaline media rapidly conducts to the formation of microspheres with an average diameter of 5 µm. SEM, TEM and AFM observations reveal that the microspheres have a hollow core of around 0.7 µm width and are composed of nanograins with an average diameter of 40 nm. These nanograins are responsible for the high specific surface area of 16 m2 g−1 deduced from nitrogen absorption/desorption isotherms, which moreover confers an important porosity to the microspheres. We believe this work may pave the way for the elaboration of a biomaterial with a large potential for therapeutic as well as diagnostic applications.

Effect of hydrophobic protein SP-C on structure and dilatational properties of the model monolayers of pulmonary surfactant

Abstract The role of hydrophobic protein SPC on the structure and dilatational rheological properties of the model monolayers of alveolar surfactant was investigated, using a developed rheological approach and atomic force microscopy (AFM) imaging. The non-equilibrium effects due to the reorganization of the cluster lipid monolayers increase with increasing protein content. The results obtained confirm the idea that the hydrophobic pulmonary proteins help to disrupt the bilayers, thereby facilitating the formation of a monolayer at the alveolar surface and the re-spreading of the collapsed phase. The properties of model lipid-protein monolayers were compared with the behaviour of a spread film of commercial seminatural surfactant Curosurf.

Hydrolysis kinetics of poly(d,l-lactide) monolayers spread on basic or acidic aqueous subphases

Abstract The hydrolysis kinetics of insoluble poly( d,l -lactide) monolayers spread on basic or acidic aqueous substrates was studied with a barostat surface balance. A theoretical approach based on the random fragmentation of polymer molecules leading to the appearance of small soluble fragments was developed. Hydrolysis rate constant values were obtained. The role of interfacial organization of the reaction products is discussed. The process of fragmentation of the interfacial polymer structures was visualized by atomic force microscopy imaging.

Self-Assembled Monolayers of Bisphosphonates: Influence of Side Chain Steric Hindrance

Bisphosphonates form self-assembled monolayers (SAMs) spontaneously on stainless steel, silicon, and titanium oxidized surfaces. We used contact angle measurements, atomic force microscopy, and X-ray reflectivity analysis to study the formation of SAMs on a model surface of ultraflat titanium (rms = 0.2 nm). The results were extended to standard materials (mechanically polished titanium, stainless steel, and silicon) and showed that water-soluble bisphosphonic perfluoropolyether can easily form SAMs, with 100% surface coverage and a layer thickness of less than 3 nm. Hydrophobic (water contact angle >110 degrees on stainless steel or titanium) and lipophobic (methylene iodide contact angle >105 degrees on titanium) properties are discussed in terms of industrial applications.

Surface characterization of poly(α-hydroxy acid) microspheres prepared by a solvent evaporation/ extraction process

This work constitutes the first attempt to characterize the wettability of poly(alpha-hydroxy acid) (PAHA) microspheres in situ, prepared according to a complex process involving emulsification, solvent evaporation, washing and freeze-drying. The analysis of the flotation profile of the microspheres has allowed us to determine both advancing and receding contact angles at the microsphere/air/water interface and furnished information on the organization of poly(vinyl alcohol) (PVA) and bovine serum albumin (BSA) at the surface of the PAHA coating. By the comparison of contact angles measured from model surfaces obtained by sampling pure PAHA, PVA, BSA and mixed PVA/PAHA monolayers on glass and poly(methyl methacrylate) (PMMA) substrates, it was concluded that the emulsifier (PVA or BSA) was strongly anchored to the surfaces of the microspheres. The use of BSA to formulate the microspheres from a single oil-in-water emulsion led to dry particles having a hydrophobic surface. The unfolding of the hydrophilic segments of the BSA embedded at the surface of the microspheres, following immersion in water, increased the wettability of the microspheres by water. The same qualitative results were obtained when PVA was used to stabilize single emulsions. On the other hand, microspheres formulated from a double water-in-oil-in-water emulsion displayed no modifications of their wettability when immersed in water. This can be explained by the absence of mobility of the hydrophilic segments of the emulsifier which are blocked in the surface or at the subsurface of the polymer matrix.

Influence of some formulation parameters on lysozyme adsorption and on its stability in solution.

According to our results concerning the behavior of lysozyme at interfaces, its secondary structure and its enzymatic activity, successful protein encapsulation would need to maintain a pH value far from the enzyme isoelectric point value during the formulation to reduce, in particular, the adsorption of lysozyme molecules at the created interfaces. Moreover, buffers or salt solution must be used in order to keep intact the native secondary conformation of lysozyme, and preserve its enzymatic activity.

Interactions between poly(ethylene glycol) and protein in dichloromethane/water emulsions: a study of interfacial properties.

From adsorption kinetics and interfacial rheological studies performed by using a pendant-drop method, i.e. in conditions close to those of the primary emulsion of the water-in-oil-in-water emulsion-encapsulation technique, it was shown that adsorption of the hen egg-white lysozyme (HEWL) at the water/dichloromethane (DCM) interface can be efficiently slowed down by modulating some parameters. It was shown that a decrease of the ionic strength of the aqueous phase, and the optimization of the density of the poly(ethylene glycol) (PEG) adsorbed film by increasing the PEG concentration or by modulating the polymer chain length, can significantly decrease the rate of adsorption of HEWL at the water/DCM interface. Moreover, it was shown that the choice of the dissolution phase of PEG (DCM or water) clearly influences the results.

Interfacial properties of amiodarone: the stabilizing effect of phosphate anions

Amiodarone, a drug used in heart therapy, is poorly soluble in water at room temperature, but forms transparent phases much more concentrated than the critical micellar concentration (CMC), when crystals are heated (above 60 degrees C) in presence of water and cooled down to room temperature. These pseudosolutions were supposed to be made of a complex system of micelles. In order to better understand the effects of pH and ion species on the supramolecular organization of amiodarone, interfacial pressure measurements were performed at the air/water interface on a Langmuir trough. Monolayers spread from chloroformic solutions over non bufferered subphases were insoluble at basic pH (NaOH, pH 10) but soluble at acidic pH (HCl, pH 4). However, a higher ionic strength obtained by adding NaCl (0.15 N) or NaH(2)PO(4) (0.15 N) to the subphase stopped the amiodarone solubilization. On an acidic phosphate subphase (NaH(2)PO(4), pH 4.4, 0.15 N), abnormally high surface pressures (>1 mN/m) were measured for high molecular areas (80-200 Å(2)/molecule) suggesting a supramolecular organization of the surface film. Insoluble monolayers were also obtained when the amiodarone supramolecular pseudosolution was spread on neutral (NaH(2)PO(4), pH 6.25, 0.15 N) or acidic (NaH(2)PO(4), pH 4.4, 0.15 N) subphases. However, a great instability on basic subphase (phosphate buffer pH 8.8) indicated the breakage of the supramolecular structure during spreading. These results are discussed taking into account the amiodarone state of ionization and the electrostatic interactions with counterions. Combining the use of phosphate counterions and that of acidic pH opens new perspectives in the optimization of amiodarone intravenous formulations.

Synthesis and characterization of CaCO3–biopolymer hybrid nanoporous microparticles for controlled release of doxorubicin

Doxorubicin (Dox) is a hydrophilic drug extensively used for treatment of breast, lung, and ovarian cancer, among others; it is highly toxic and can cause serious side effects on nontargeted tissues. We developed and studied a hybrid nanoporous microparticle (hNP) carrier based on calcium carbonate and biopolymers derivatized with folic acid (FA) and containing Dox as a chemotherapeutic drug model. The hNPs were characterized by X-ray diffraction, and Raman and Fourier transform infrared (FTIR) spectroscopies. The X-ray diffraction patterns of calcium carbonate particles showed about 30-70% vaterite-calcite polymorphisms and up to 95% vaterite, depending on the absence or the presence of biopolymers as well as their type. Scanning electron microcopy images revealed that all types of hNPs were approximately spherical and porous with average diameter 1-5 μm, and smaller than CaCO3 microparticles. The presence of biopolymers in the matrices was confirmed after derivatization with a fluorescein isothiocyanate probe by means of confocal microscopy and FTIR synchrotron beamline analysis. In addition, the coupling of lambda carrageenan (λ-Car) to FA in the microparticles (FA-λ-Car-hNPs) increased the cancer-cell targeting and also extended the specific surface area by up to ninefold (26.6 m2 g(-1)), as determined by the Brunauer-Emmett-Teller isotherm. A nanostructured porous surface was found in all instances, and the FA-λ-Car-hNP pore size was about 30 nm, as calculated by means of the Barrett-Joyner-Halenda adsorption average. The test of FA-λ-Car-hNP anticancer activity on human osteosarcoma MG-63 cell line showed cell viabilities of 13% and 100% with and without Dox, respectively, as determined by crystal violet staining after 24 h of incubation.

Spectroscopic studies on poly(ethylene glycol)-lysozyme interactions

In the present paper, different spectroscopic methods were applied to evaluate conformational changes of hen egg-white lysozyme (HEWL) in various solvents and in the presence of poly(ethylene glycol) (PEG). In citrate (0.007M, pH=6), or in Tris (0.1M, pH=7.4), no conformational change of the protein was measured across the range of concentrations tested. In addition, HEWL in ultra-pure water revealed no irreversible conformational change and no activity loss, at least at low concentrations (< or =0.2mg/ml). Whereas PEG can induce a reorganization of water molecules, no change of the secondary and tertiary protein conformations was observed in the presence of PEG. In addition, in the presence of PEG of various molecular weights, no change of enzymatic activity of the HEWL was observed across the range of concentrations tested.