Saha Debasish, Testard Fabienne, Grillo Isabelle, Zouhiri Fatima, Desmaele Didier, Radulescu Aurel, Desert Sylvain, Brulet Annie, Couvreur Patrick, Spalla Olivier
CEA Saclay, DSM/IRAMIS/NIMBE/LIONS, UMR CEA/CNRS 3299, 91191 Gif sur Yvette, France.
Soft Matter. 2015 Jun 7;11(21):4173-9. doi: 10.1039/c5sm00592b.
Squalene based nanoparticles obtained via nanoprecipitation are promising candidates as efficient anti-cancer drugs. In order to highlight their preparation process and to facilitate further clinical translation, the present study enlightens the paramount role of the solvent in the formation of these nanomedicines. Three different squalene-based nanoparticles, i.e. squalenic acid, deoxycytidine squalene and gemcitabine squalene, have been investigated before and after organic solvent evaporation. Size and structural analysis by Small Angle Neutron Scattering revealed that droplets' size was uniquely controlled by the solvent composition (ethanol-water), which evolved during their gradual formation. The particles were preferably swollen by water and the swelling increased when less ethanol was present. Either coalescence or fragmentation was observed depending on the increase or decrease of the ethanol content, supporting an equilibrium control of the size. Moreover, a high water swelling was observed for the three local organization of the nanodroplets (hexagonal for gemcitabine squalene, cubic for deoxycytidine and not structured for squalenic acid) and could be the source of the previously reported efficiency of related anti-cancer squalene based nanomedicines.
通过纳米沉淀法获得的基于角鲨烯的纳米颗粒有望成为高效抗癌药物的候选者。为了突出其制备过程并促进进一步的临床转化，本研究阐明了溶剂在这些纳米药物形成过程中的关键作用。在有机溶剂蒸发前后，对三种不同的基于角鲨烯的纳米颗粒，即角鲨烯酸、脱氧胞苷角鲨烯和吉西他滨角鲨烯进行了研究。小角中子散射的尺寸和结构分析表明，液滴尺寸由溶剂组成（乙醇-水）唯一控制，在其逐渐形成过程中溶剂组成会发生变化。颗粒优先被水溶胀，当乙醇含量减少时溶胀增加。根据乙醇含量的增加或减少，观察到了聚结或破碎现象，这支持了对尺寸的平衡控制。此外，对于纳米液滴的三种局部结构（吉西他滨角鲨烯为六方结构，脱氧胞苷为立方结构，角鲨烯酸无结构）都观察到了高水溶胀现象，这可能是先前报道的相关基于角鲨烯的抗癌纳米药物具有疗效的原因。
