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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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A well-defined poly(ethylene glycol) methyl ether-b-poly(lactic acid) copolymer (mPEG-PLA) featuring a new, Y-shaped, architecture with a hydroxyl functional group between the two blocks has been prepared and thoroughly characterized. The functional copolymer was then readily coupled to diglycolyl-cabazitaxel. The resulting copolymer conjugates assembled into stable and monodisperse nanoparticles (NPs) in aqueous suspension. The architecture of the copolymer conjugate is shown to impact the spatial distribution of the drug within the nanoparticles. With the Y-shaped architecture, cabazitaxel was found localized at the interface of the hydrophobic PLA core and the hydrophilic mPEG corona of the NPs, as substantiated by variable temperature NMR analysis of the nanoparticles in D2O. Preliminary in vitro release studies reveal dependence on the architecture of the copolymer conjugate. This new approach offers promising perspectives to finely tune the position of the active ingredient in polymeric nanoparticles.

Multifunctional poly­(ethylene glycol)-block-poly­(lactic acid) (PEG-b-PLA) nanoparticles for cancer cell targeting and imaging have been designed by a combination of ring-opening polymerization and “click” chemistry. Nanoparticles containing both a targeting ligand and a fluorescent probe were prepared by blending PLA-b-PEG–ligand, PLA-b-PEG–fluorescent probe, and PLA-b-PEG–OMe copolymers at the molar ratios necessary to achieve the desired surface ligand and fluorescent probe densities. This strategy has been illustrated by the preparation of a large library of a variety of nanoparticles, such as ligand-decorated nanoparticles (with biotin, folic acid or anisamide), fluorescent nanoparticles (UV–vis or near-infrared dyes), and multifunctional nanoparticles decorated with a targeting ligand and a fluorescent probe. Successful targeting was demonstrated by surface plasmon resonance and in vitro experiments on different cancer cell lines.

The temperature dependence of the formation of a complex between an alpha-d(CCTTCC) hexanucleotide and its complementary beta-d(GGAAGG) sequence was studied and compared to the formation of the beta-d(CCTTCC):beta-d(GGAAGG) complex. Such alpha-beta complex is more stable than the regular beta:beta complex. The Tm value for the alpha:beta complex is 28 degrees C (delta G degrees = -7.3 kcal/mole) while Tm = 20, 1 degree C (delta G degrees = -6.3 kcal/mole) for the beta:beta complex. The stoechiometry of the alpha:beta complex corresponds to the formation of a 1:1 duplex. However, when the alpha- strand is made of alpha-purines: alpha-d(GGAAGG), the stability of the alpha:beta complex, alpha-d(GGAAGG):beta-d(CCTTCC) is found to be lower (Tm = 13.8 degrees C) than the stability of the regular beta-beta complex, leading to the conclusion that the nature of the alpha-sequence is important in terms of stability when considering the synthesis of such a sequence for using it as antisense oligonucleotide.