[Risk of deep venous thrombosis during an air flight: prevention and counselling at the counter]. / Le risque de thrombose veineuse profonde lors d'un voyage en avion : prévention et conseil à l'officine.

Worldwide air traffic reaches about 2.3 billion passengers per year. The increasing number of persons at thrombo-embolic risk, together with potentially severe or fatal complications of deep venous thrombosis, suggests community pharmacists can give basic preventive advice to persons identified as at risk.

Improvement of an encapsulation process for the preparation of pro- and prebiotics-loaded bioadhesive microparticles by using experimental design.

The purpose of this study was to design a new vaginal bioadhesive delivery system based on pectinate-hyaluronic acid microparticles for probiotics and prebiotics encapsulation. Probiotic strains and prebiotic were selected for their abilities to restore vaginal ecosystem. Microparticles were produced by emulsification/gelation method using calcium as cross-linking agent. In the first step, preliminary experiments were conducted to study the influence of the main formulation and process parameters on the size distribution of unloaded microparticles. Rheological measurements were also performed to investigate the bioadhesive properties of the gels used to obtain the final microparticles. Afterwards an experimental design was performed to determine the operating conditions suitable to obtain bioadhesive microparticles containing probiotics and prebiotics. Experimental design allowed us to define two important parameters during the microencapsulation process: the stirring rate during the emulsification step and the pectin concentration. The final microparticles had a mean diameter of 137µm and allowed a complete release of probiotic strains after 16h in a simulated vaginal fluid at +37°C.

Evaluation of gliadins nanoparticles as drug delivery systems: a study of three different drugs.

In this paper, biopolymer nanoparticles are studied, which unlike many synthetic carriers used for controlled release, are biocompatible and biodegradable systems. Gliadins nanoparticles are obtained by a desolvatation method, also known as drawning-out precipitation. These particles have been shown to be interesting as drug release systems for all-trans-retinoic acid. The aim of this paper was to study the influence of the polarity of different drugs on nanoparticle characteristics such as size and drug loading efficiency. Three drugs of three different polarities were studied: the hydrophobic Vitamin E (VE), the slightly polar mixture of linalool and of linalyl acetate (LLA) and the cationic amphiphilic benzalkonium chloride (BZC). This comparative work shows that the amount of the entrapped VE and LLA is higher than that of the cationic BZC, confirming a strong interaction between gliadins and apolar compounds, due to the apolarity of the proteins. This interaction results in a low diffusion coefficient and a partition coefficient in favour of gliadins, resulting in a low permeability coefficient. The drug release kinetics of two substances, LLA and BZC, are observed, in showing a burst effect, then a diffusion process, which can be modelled assuming that the particles are homogeneous spheres.

Alpha-tocopherol encapsulation and in vitro release from wheat gliadin nanoparticles.

Alpha-tocopherol, or vitamin E (VE), is widely used as a strong antioxidant in many medical and cosmetic applications, but is rapidly degraded, because of its light, heat and oxygen sensitivity. Thus, all of its formulation has to avoid contact with light, heat or air. Drug loaded carriers are an attractive opportunity, especially if they are made for bioacceptable macromolecules such as vegetal proteins. For instance, gliadins, extracted from wheat gluten, generate nanoparticles by a desolvatation method and may interact with epidermal keratin for therapeutic or cosmetic formulations. Their lipophilic drug loading capacities have been investigated. The VE loaded gliadin nanoparticles have been characterized by their size, by their zeta potential, by their VE payload, and by their entrapment efficiency. When VE loaded, the gliadin particle size is approximately 900 nm and their charge is close to zero. They are suitable VE drug carriers with an optimum encapsulation rate approximately 100 VE microg/gliadin mg with an efficiency of more than 77%. The release behaviour of VE loaded nanoparticles may be interpreted as a 'burst effect', followed by a diffusion process through an homogeneous sphere.

Adaptive immune responses of legumin nanoparticles.

Legumin is one of the main storage proteins in the pea seeds (Pisum sativum L.) and the molecules of this protein have the capacity of binding together to form nanoparticles after aggregation and chemical cross-linkage with glutaraldehyde. The aim of this work was to study the adaptive immune response of legumin nanoparticles in rats. Following intradermal immunisation with the native protein legumin and legumin nanoparticles of about 250 nm, the humoral and cell-mediated immune responses were analysed in rats. The humoral responses against legumin and legumin nanoparticles were examined by western blot and ELISA analysis. Both techniques clearly showed that sera from rats immunised with legumin strongly expressed antibodies against this protein. On the contrary, serum samples from rats inoculated with legumin nanoparticles did not contain detectable amounts of antibodies. These results may be explained by a reduction on the antigenic epitopes of the protein induced by the glutaraldehyde used during the cross-linking step. Concerning the cell-mediated response, neither legumin nor legumin nanoparticles stimulated an immunogenic response. This absence of response of spleen lymphocytes for legumin and legumin nanoparticles may be explained by a cytostatic effect of legumin which was corroborated by the evaluation of the middle phase of cell apoptose. In fact, both legumin and legumin nanoparticles are potent inductors of a cytostatic phenomenon and showed a significant increase of the chromatin condensation (p < 0.05) as compared with control.

Effects of encapsulation of primidone on its oxidative metabolism in rats.

The aim of this study was to evaluate the influence of primidone (PRM) nanoencapsulation on its metabolism. Suspensions of PRM powder and PRM-loaded poly-epsilon-caprolactone nanocapsules were administered orally in the same way to rats. Primidone-loaded poly-epsilon-caprolactone nanocapsules were prepared according to the interfacial deposition technique. Free PRM suspensions were obtained by addition of PRM powder to a suspension of 0.212% carboxymethylcellulose CMC 12H in water. The dose was 20 mg/kg, n = 6, for each experiment. Urinary and faecal levels of PRM and of its three major metabolites, phenylethylmalonamide (PEMA), phenobarbital (PB), and p-hydroxyphenobarbital (p-HO-PB), were determined. Concentrations were evaluated by high-performance liquid chromatography (HPLC) according to a validated analytical method. After PRM nanocapsule administration, non-metabolised PRM urinary levels were increased compared to those observed after administration of a suspension of primidone powder (43.7+/-8.8% after PRM-loaded nanocapsule and 37.7+/-8.1% after free PRM administration). For phenylethylmalonamide, no difference was observed in urinary excretion in the two cases. For two of the oxidised metabolites, PB and p-HO-PB, excretion was delayed and shortened. The amount of these oxidised metabolites was lowered from 0.95% after free PRM administration to 0.25% after PRM-loaded nanocapsule administration. No difference was noted in non-metabolised primidone excretion in faeces. These results suggest that primidone-loaded nanocapsules could be used as a vehicle for oral primidone administration in order to minimise the phenobarbital metabolic pathway.

[Wheat gliadin nanoparticle size control by determination of the solubility parameters of these plant proteins]. / Maîtrise de la taille de nanoparticules de gliadines de blé par la détermination de leur paramètre de solubilité.

Gliadins nanoparticles, protein complex from wheat gluten, were prepared by coacervation (macromolecules desolvatation). The objective was to prepare nanometric colloidal systems whith both smallest particle size and polidispersity index. Macromolecules solvent choice is predominant. Their total solvatation enables of control the desolvatation process and thence particle sizes. Different pharmaceutical solvents were assayed. In order to select the best of them, a thermodynamical approach was used. It rests on the determination of the solubility parameter delta G of the gliadins complex. The best solvent is the one whose solubility parameter (calculated or experimentally determined) is equal to the plant protein's.

Bioadhesive potential of gliadin nanoparticulate systems.

The objective of this work was to prepare, characterise and evaluate the adhesive potential of gliadin nanoparticulate carriers. Firstly, lectin-nanoparticle conjugates were obtained by the carbodiimide (CDI) covalent binding of Dolichos biflorus lectin (DBA) to the surface of gliadin nanoparticles (NP) containing carbazole (as a model lipophilic drug). The DBA binding efficiency was favoured in mild acidic conditions. Similarly, a CDI concentration of about 0.63 mg/mg nanoparticles, acting during at least 1 h, provided binding efficiencies of about 50% bulk lectin. Under optimised experimental conditions, the DBA conjugates showed a size of around 500 nm and the amount of loaded carbazole and the DBA content were calculated to be around 15 and 23.5 microg/mg, respectively. The bioadhesive activity of NP and DBA conjugates was determined in samples of small and large rat intestinal mucosa. The amount of adsorbed NP was calculated to be around 8 and 4 g/m(2) in the small and large intestine, respectively. This high capacity to interact with the mucosa may be explained by gliadin composition. In fact, gliadin is rich in neutral and lipophilic residues. Neutral amino acids can promote hydrogen bonding interactions with the mucosa, while the lipophilic components can interact with the biological tissue by hydrophobic interactions. The bioadhesive activity of DBA conjugates was calculated to be about 2 g/m(2) in the small intestine and greater than 4 g/m(2) in the caecum and distal colon. These degrees of interaction were always significantly higher than those obtained with controls. Finally, DBA did not provide the specificity for interaction with Peyer's patches. In summary, gliadin nanoparticles show a high capacity of non-specific interaction with the intestine, whereas DBA binding to the surface of these carriers provided a greater specificity for colonic mucosa.

Primidone-loaded poly-epsilon-caprolactone nanocapsules: incorporation efficiency and in vitro release profiles.

This paper describes the preparation of primidone-loaded poly-epsilon-caprolactone nanocapsules according to the interfacial deposition technique. The colloidal suspension obtained showed a monomodal size distribution with a mean diameter ranging from 308 to 352 nm. By adjusting the process parameters, the encapsulation efficiency was about 74% with good reproducibility. Primidone release from the nanocapsules was found to be slower as compared to the oily control solution despite an important burst-effect. The release profile was not influenced by the pH of the release medium.

Preparation of Ulex europaeus lectin-gliadin nanoparticle conjugates and their interaction with gastrointestinal mucus.

One approach to improve the bioavailability and efficiency of drugs consists of the association of a ligand (i.e. lectins), showing affinity for biological structures located on the mucosa surfaces, to nanoparticulate drug delivery systems. In this context, Ulex europaeus lectin-gliadin nanoparticle conjugates (UE-GNP) were prepared with the aim of evaluating their in vitro bioadhesive properties. The lectin was fixed by a covalent procedure to gliadin nanoparticles by a two-stage carbodiimide method. Typically, the amount of bound lectin was calculated to be approximately 15 microg lectin/mg nanoparticle, which represented a coupling efficiency of approximately 16% of the initial lectin concentration. In addition, the activity of these conjugates was tested with bovine submaxillary gland mucin (BSM) and the level of binding to this mucin was always much greater with UE-GNP than with controls (gliadin nanoparticles). However, the presence of 50 micromol fucose, which is the reported specific sugar for U. europaeus lectin, specifically inhibited the activity of these conjugates and, therefore, the UE-GNP binding to BSM was attenuated by 70%. These results clearly showed that the activity and specificity of U. europaeus lectin was preserved after covalent coupling to these biodegradable carriers.

Entrapment efficiency and initial release of phenylbutazone from nanocapsules prepared from different polyesters.

Several formulations of poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA) nanocapsules containing phenylbutazone were prepared according to the interfacial deposition technique. These formulations differed in the type of polymer used to form the shell of the nanocapsules. Analysis of particle size distribution and encapsulation efficiency of the nanocapsules revealed that the type and molecular weight of polyester used were the main factors influencing these properties. PLA had the highest encapsulation efficiency with the best reproducibility. From in vitro release studies, a small amount of drug release was observed at pH 7.4. However, in the gastric medium, an important burst effect occurred and was highest with the PLGAs and lowest with PCL, suggesting that drug release from these systems is affected by the type of polymer and the environmental conditions. The two formulations of phenylbutazone-loaded nanocapsules should be evaluated based on PCL and PLA in vivo in order to determine to what extent they are able to reduce the local side effects of this drug.

Properties of glutaraldehyde cross-linked vicilin nano- and microparticles.

The influence of some selected factors on the properties of nano- and microparticles obtained from vicilin (storage protein from Pisum sativum L.) has been studied. These systems were prepared by coacervation followed by a cross-linking step with glutaraldehyde. Stabilized vicilin particles could be formed very rapidly after a short exposure to a low glutaraldehyde concentration. Nevertheless, particles increased in size with time of reaction and with an increase in glutaraldehyde concentration. On the other hand, the cross-linking process greatly influenced particle stability when incubated in the presence of trypsin. In this case, degradation followed a square-root-time relationship, suggesting enzymatic attack at the surface and in the interior of the matrix. The influence of the particle size on the tryptic degradation was also investigated and led to similar conclusions. Thus, microparticles showed a more rapid degradation than might be anticipated considering particle diameter alone.

GC-MS determination of phenobarbitone entrapped in poly-epsilon-caprolactone nanocapsules.

In order to evaluate the concentration of a hydrophilic drug, phenobarbitone, in a suspension of poly-epsilon-caprolactone nanocapsules, a gas chromatographic-mass spectrometric procedure, performed after methylation of the drug, was developed and validated. Free phenobarbitone (in solution in the liquid phase), released phenobarbitone (after opening the nanocapsules with ethyl acetate) and total entrapped phenobarbitone (after extraction with methylene chloride), were measured. Experimental results for four lots with various concentrations showed that the highest preparation of entrapped drug (80%) was obtained for a total concentration of 3.64 mg ml-1 in the nanocapsule suspension.

Determination of alpha-bisabolol and d-panthenol in cosmetic products by gas chromatography.

Synopsis alpha-bisaboloi and d-panthenol are used in many cosmetic preparations, respectively, for their anti-inflammatory and regenerating properties. Their quantitative determination was an important element of their evaluation in these emulsions. Their concentration has been determined by gas chromatographic techniques, using a flame ionization detector. In both cases, the internal standards have been chosen for their compatibility with the analysis of extracted substances. Owing to the complexity of the cosmetic formulations, a preliminary extraction of alpha-bisabolol and d-panthenol was necessary. For the two substances the preparative separation was based on a liquid-liquid extraction. After dissolving the emulsion in methanol and diluting it with an aqueous buffer solution alpha-bisabolol was then extracted by ethyl acetate and d-panthenol by ethyl formate.

Viscoelastic properties of paracrystalline phases appearing in water-surface agent-oil diagrams.

Synopsis The ternary mixtures investigated were obtained from water, mineral oil and ether-linked non-ionic surfactants (polyoxyethylene derivatives of oleic alcohol). The examination of the rheological properties of these mixtures, particularly the viscoelastic properties of the various phases encountered in these diagrams, was expanded. The phases examined were: - anisotropic paracrystalline phases: hexagonal phase and lamellar phase; - the isotropic paracrystalline phase: type I viscous isotropic phase. The measurement instrument used for this work was a creep rheometer. The paracrystalline phases were subjected to very low shear stresses, and the strains induced were recorded as a function of time. The analysis of creep functions obtained enabled us to construct a viscoelastic model and obtain the value of its parameters for each particular case. This analysis of the viscoelastic properties provides an accurate identification of each of the paracrystalline phases: the lamellar and isotropic viscous phases show respectively a Newtonian fluid nature with a yield value (Bingham model), and a perfect elastic solid. The hexagonal phase on the other hand shows an intermediate type of behaviour which is characterized by a well-defined retarded elasticity. This study could also lead to a microscopic interpretation of their structure.