Al Haj et al. evaluated TMX-loaded solid #MK-1775 solubility dmso randurls[1|1|,|CHEM1|]# lipid nanoparticles for parenteral administration, and, though promising, these systems required a sophisticated preparation method because they were elaborated by high pressure homogenization technique [40]. Instead of this, the ease of preparation is a common ME characteristic. Tagne et al. evaluated a nanoemulsion containing TMX that has a significantly better in vitro performance reducing cell proliferation when compared to a TMX-loaded suspension. However, they have used a concentration of TMX equal to 3 × 10-5M for Inhibitors,research,lifescience,medical all the cell culture treatments, while our MEs were able to solubilize more than 100-fold higher

of TMX [6]. These authors claimed for an important cellular uptake because of the nanometric sizes of the nanoemulsions. Similar results could be expected with our formulations but the

in vivo therapeutic parameters would be improved because of the Inhibitors,research,lifescience,medical drug concentration achieved. Another important difference between both works is the technique of preparation. They used a microfluidizer processor Inhibitors,research,lifescience,medical which provides a resultant high shear rate by accelerating the product through microchannels to a high velocity for size reduction to the nanoscale range. They previously prepared a suspension of TMX and then the mixture was homogenized. On the contrary, MEs involve a spontaneous process of formation for a defined composition and the selection of the composition is searched through a screening of components. As a result of these two different techniques they found a negative z potential while we observed no charges on the droplets’ layers. Another consequence was that they obtained a Inhibitors,research,lifescience,medical bimodal distribution of mean droplet sizes; on the contrary, we observed a more uniform distribution. In conclusion, the above-mentioned differences are in relation with the fact that Tagne et al. have prepared nanoemulsions, while our work deals on MEs; it is very clear in literature the differences between them independently that they could have Inhibitors,research,lifescience,medical similar compositions and mean droplet size [4, 8, 41]. More

recently, the electrospray technique was proposed to produce TMX-loaded poly(amidoamine)-cholesterol conjugate nanoparticles in powder form without any excipient in a single step. Spite of this, the nanoparticles showed sizes much higher than 200nm and a drug loading of about 40% [27]. It is also necessary to remark that the cell culture experiments were carried out with no reagent addition; this is a very important issue because previous report [27, 42] found that MCF7 cells are highly sensitive towards DMSO. Indeed, volumes equal to or higher than 2μL (2% v/v) result in a cytotoxic effect that partially overlaps the one observed in cells treated with free TMX diluted in DMSO. Therefore, this “background” cytotoxicity leads to an overestimation of the free TMX activity.

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