The preparation of nanoparticles by emulsion solvent evaporation is a very popular method. The purpose of the present study was to clarify the mechanism by which nanoparticles of ethylcellulose (EC) and poly(lactic acid) (PLA) are formed during the emulsion solvent evaporation procedure. This study was mainly based on the measure of the variation of the emulsion and nanoparticle surface charge and size during the solvent evaporation process. From the data obtained and depending on the polymer used (EC or PLA), two different models are proposed to explain the nanoparticle formation. In the EC model, after shrinkage of the emulsion droplets as the direct consequence of solvent evaporation, coalescence occurred before stable and solvent-free nanoparticles were formed. On the contrary, in the PLA model, no or limited coalescence was found to occur so that the picture is that one PLA nanoparticle originated from one (or only a few) PLA emulsion droplet after its shrinkage.

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Background This study aimed to investigate compounds acting on the host cell machinery to impair parasite installation with the possible advantage of limiting drug resistance. The strategy therefore consisted of selecting compounds that are poorly active on the axenic parasite, but very active on the intramacrophage form of Leishmania. Objectives To identify a drug candidate from focused screening of adamantamine derivatives that can inhibit the development of Leishmania infantum in macrophages. Methods In vitro screening was performed on a library of 142 adamantamine derivatives with axenic and intramacrophage forms of L. infantum, as well as cytotoxicity assays, allowing selection of the most promising compound. Absorption, distribution, metabolism and excretion (ADME) experiments, including pharmacokinetics and microsomal stability, were performed and finally the physicochemical stability of the compound was investigated to assess its suitability for further drug development. Results VP343 was identified first in vitro, with a CC50 value of 63.7 μM and an IC50 value of 0.32 μM for L. infantum intramacrophage amastigotes and then in vivo, with a 59% reduction of the liver parasite burden after oral administration at 10 mg/kg/day for 5 days. In addition, the ADME data were compatible with moving this compound further through the antileishmanial drug candidate pipeline. Conclusions VP343 has the properties of a good drug candidate and merits further investigations.