Preparation of organic nanoparticles using microemulsions: their potential use in transdermal delivery.

Organic nanoparticles of cholesterol and retinol have been synthesized in various AOT (Aerosol OT; sodium bis(2-ethylhexyl) sulfosuccinate)/heptane/water microemulsions by direct precipitation of the active principle in the aqueous cores. The nanoparticles are observed by transmission electron microscopy (TEM) using the adsorption of a contrasting agent, such as iodine vapor. The size of the nanoparticles can be influenced, in principle, by the concentration of the organic molecules and the diameter of the water cores, which is related to the ratio R=[H2O]/[surfactant]. The particles remain stable for several months. The average diameter of the cholesterol nanoparticles varies between 3.0 and 7.0 nm, while that of retinol varies between 4.0 and 10 nm. The average size of the cholesterol nanoparticles does not change much either as a function of the ratio R or as a function of the concentration of cholesterol. The constant size of the nanoparticles can be explained by the thermodynamic stabilization of a preferential size of the particles. Chloroform is used to carry the active principle into the aqueous cores. Retinol molecules form J-complexes composed of two or three molecules, as detected by UV-visible spectroscopy.

Mechanism of formation of inorganic and organic nanoparticles from microemulsions.

This chapter essentially deals with the preparation of nanoparticles using microemulsions. The preparation of inorganic nanoparticles--Ni2B, Pt, Au, Pt-Au, AgX--and the synthesis of organic nanoparticles--cholesterol, rhovanil, rhodiarome--are systematically studied as a function of the concentration of the precursor molecules, the size of the inner water cores, and the manner of mixing the various solutions. Two different behaviors are observed in the various systems. The first case shows a dependence of the nanoparticle size on the various physicochemical parameters. Either a monotonous increase of the size or the presence of a minimum is observed as a function of the concentration of the precursor molecules. This case can be easily explained following the LaMer diagram, where the nucleation of the nanoparticles is separated from the particle growth. The second case does not show any dependence of the nanoparticle size on the physicochemical parameters. The size remains constant in all experimental conditions. The constant character of the size can be explained only by thermodynamic stabilization, where particles with a certain size are better stabilized. It should be emphasized that the size distribution is small in all the cases studied. Finally, the aging of the nanoparticles was also checked, especially for the organic nanoparticles. It is concluded that these particles remain stable for months in the microemulsion.

Synthesis of monodisperse nimesulide nanoparticles in microemulsions E170/isopropyl myristate/water/n-butanol (or isopropanol).

Nanoparticles of nimesulide have been synthesized in two systems of microemulsion: E170/isopropyl myristate/water/n-butanol (or isopropanol). Nanoparticles are monodisperse. In the two microemulsions, the size of the nanoparticles is comprised between 45 and 60 A and also seems to be independent of the factor R ([water]/[E170]) and of the concentration of the nimesulide solubilized in chloroform. The constancy of the size suggests that the size is controlled by thermodynamic stabilization of the nanoparticles with the surfactant. The nature of the cosurfactant does not have an obvious influence on the nanoparticle size. The nanoparticles are instantaneously formed and stay stable during a long period of time (several months).