Jacques-Emile Proust

Physico-chemical stability of colloidal lipid particles

Recent advances in nanoparticle systems for improved drug delivery display a great potential for the administration of active molecules. Generally, the lipid systems presented the advantage of their low toxicity due to their composition of physiological lipids compared to polymeric particles. The physico-chemical stability of the lipid carriers showed variations due to their numerous compositions and structures. This review consequently focuses on the physico-chemical stability of dispersions in the nanometer range where the lipids are the main or the only components. It highlights on the destabilization mechanisms, the techniques used to detect this destabilization and the inductors of the destabilization. Finally, the methods used to optimize the stability of lipid nanoparticle systems are described in the last part.

A Novel Phase Inversion-Based Process for the Preparation of Lipid Nanocarriers

AbstractPurpose. To develop and subsequently evaluate a novel phase inversion-based method used to formulate lipidic nanocapsules. Methods. Mechanical properties of emulsions prepared by multi-inversion phase processes were investigated using a drop tensiometer. Based on the results obtained, a formulation process was developed and a new type of nanocarrier was prepared. These particulates were sized by photon correlation spectroscopy and were visualized by atomic force microscopy and transmission electronic microscopy. Differential scanning calorimetry was also performed. Results. The marginally cohesive but stable interfacial properties of the initial system led to the formulation of lipidic nanocapsules that were composed of a liquid core surrounded by a cohesive interface and were dispersed in an aqueous medium. These related suspensions were stable upon dilution for several months. The control of the formulation parameters allowed an adjustment of the particle mean diameter in the range of 25-100 nm with a monodisperse size distribution. Conclusions. A novel and convenient process for the preparation of lipidic nanocapsules is described. The structure of these particulates resembles a hybrid between polymeric nanocapsules and liposomes. Such nanocapsules display a strong potential for drug delivery.

Why does PEG 400 co-encapsulation improve NGF stability and release from PLGA biodegradable microspheres?

AbstractPurpose. The aim of this work was to understand the mechanism by which co-encapsulated PEG 400 improved the stability of NGF and allowed a continuous release from PLGA 37.5/25 microspheres. Methods. Microparticles were prepared according to the double emulsion method. PEG 400 was added with NGF in the internal aqueous phase (PEG/PLGA ratio 1/1 and 1.8/1). Its effect was investigated through interfacial tension studies. Protein stability was assessed by ELISA. Results. A novel application of PEG in protein stabilization during encapsulation was evidenced by adsorption kinetics studies. PEG 400 limited the penetration of NGF in the interfacial film of the primary emulsion. Consequently, it stabilized the NGF by reducing the contact with the organic phase. In addition, it avoided the NGF release profile to level off by limiting the irreversible NGF anchorage in the polymer layers. On the other hand, the amount of active NGF released in the early stages was increased. During microparticle preparation, NaCl could be added in the external aqueous phase to modify the structure of microparticles. This allowed to reduce the initial release rate without affecting the protein stability always encountered in the absence of PEG. Conclusions. PEG 400 appeared of major interest to achieve a continuous delivery of NGF over seven weeks from biodegradable microparticles prepared by the double emulsion technique.

The influence of lipid nanocapsule composition on their size distribution.

A formulation process, based on the inversion phase of an emulsion, was used to prepare lipid nanocapsules. Triglycerides, lecithin, salted water and hydroxy stearate of poly(ethylene glycol) were used in the preparation. The amounts of each that allowed nanocapsules to be formed described a feasibility domain within a ternary diagram. The size distribution of various nanoparticulate carriers has already been shown to influence their applications. An experimental mixture design inside the feasibility domain has been used in order to approximate, through an empirical model, the influence of the quantitative composition of nanocapsules on their size distribution. Reduced cubic polynomial equations successfully modelled the evolution of responses in terms of particle average diameters and coefficients of variation. The results were presented using an analysis of response surface showing a scale of possible particle sizes between 20 and 95 nm and a coefficient of variation between 11 and 40%. Furthermore, this technique showed that the proportion of hydrophilic surfactant had a major influence on the average diameter and the size distribution of the particles decreasing when its proportion increased. On the contrary, the coefficient of variation and the average diameter slightly increase with the proportion of triglycerides. Such a tool offers major advantages to design the formulation of particles as a function of the required size distribution.

Development and characterization of solid lipid nanoparticles loaded with magnetite

This paper describes the preparation of colloidal lipid particles containing magnetite from warm emulsions. A two step method was used to obtain the nanoparticles: (i) formulation of a transparent phase by heating a O/W emulsion (aqueous surfactant solution melted with a lipid phase, containing the ethyl oleate and soybean lecithin) in which modified lipophilic magnetite is incorporated, and (ii) preparation of the nanoparticles by dispersing the warm transparent phase in cold water (7 degrees C) under mechanical stirring. The latter method gives spherical nanoparticles of a mean size of 62 nm measured by Photon Correlation Spectroscopy and Transmission Electronic Microscopy. The magnetite entrapment efficiency was determined by use of a magnetophoretic sedimentation method.

Behavior of pure and mixed DPPC liposomes spread or adsorbed at the air-water interface

Liposomes from pure dipalmitoylphosphatidylcholine (DPPC) and mixed DPPC: distearoylphosphatidylcholine (DSPC): soybean lecithin (SL) prepared by the Bangham method with sonication were dispersed into solution or spread at the interface and the kinetics of the surface film formation was studied by measuring and recording the evolution of superficial tension, surface potential, and superficial (14C labeled) DPPC density.A simple theoretical approach can describe these kinetics by two processes: irreversible diffusion of closed vesicles into or from the bulk phase, and irrevers ible transformation of closed spherical vesicles into destroyed ones which form the surface film. Diffusion controls the phenomenon for small initial amounts of liposomes.Transformation controls the phenomenon for important initial amounts of liposomes. The kinetic constant of the transformation,K, does not depend on the technique used to form the surface film (spreading or adsorption).The equilibrium and rheological properties of surface films formed after liposome spreading are compared to those of monolayers

Interfacial stability of lipid nanocapsules

Abstract In order to obtain information on the structure and the stability of lipid nanoparticles, interfacial films, made from their spreading, were studied at the air/water interface. The related results were compared with the spreading of their individual components at the same interface. The interfacial behaviour of the particles indicated a nanocapsule structure with an oily core surrounded by a surfactant layer. Unlike liposomes or high density lipoproteins (HDL), no destruction leading to the release of their core was observed during their spreading and compression. Moreover, the sampling of the nanoparticle films at the air/water interface deposited on mica plate depicted by atomic force microscopy (AFM) showed entire nanocapsules. This stability is attributed to their surface cohesion related to their surfactant shell. Indeed, a partial particle surface “erosion” occurred leading to the spread of a certain amount of less attached hydrophilic surfactant molecules without releasing the nanocapsule lipid content. This study illustrates that the Langmuir balance can be used as a tool for studying the general organisation of lipid particles. Moreover, this method may allow the determination of the release profile of some encapsulated drugs.

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.

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.