The purpose of this study was to show whether it is possible to prepare sub 100 nm or preferably sub-50 nm drug nanosuspension (NS) of suitable quality for intravenous administration. Furthermore, we have studied how the brain targeting potential of such small size organic NS differs from relatively bigger size NS. Two combination technologies (cavi-precipitation, H96) and a standard high-pressure homogenization (HPH) technology were used to prepare drug NS of different sizes. The cavi-precipitation process generated the smallest AmB NS, i.e., 27 nm compared to 79 nm by H96 technology and 252 nm by standard HPH technology. Dialysis of the nanosuspension in the original dispersion media was found to be the most efficient solvent removal method without negatively affecting particle size. The removal of organic solvent was found to drastically improve the stability of the formulations. The protein adsorption pattern shows that the small size NS particles obtained by the cavi-precipitation process have the potential to circulate longer in the bloodstream and have the potential to be taken up by the blood–brain barrier. The cavi-precipitation process generated ultrafine NS particles, which fulfilled the quality requirements for intravenous administration and offer a potential solution for brain targeting.

本研究的目的是展示是否有可能制备适合静脉内给药的质量低于 100 nm 或优选低于 50 nm 的药物纳米混悬液 (NS)。此外，我们研究了这种小尺寸有机 NS 的大脑靶向潜力与相对较大尺寸的 NS 有何不同。两种组合技术（腔沉淀，H96）和一种标准的高压均质（HPH）技术被用于制备不同尺寸的药物NS。空腔沉淀过程产生了最小的 AmB NS，即 27 nm，而 H96 技术为 79 nm，标准 HPH 技术为 252 nm。发现在原始分散介质中透析纳米悬浮液是最有效的溶剂去除方法，不会对粒径产生负面影响。发现有机溶剂的去除显着提高了制剂的稳定性。蛋白质吸附模式表明，通过腔沉淀过程获得的小尺寸 NS 颗粒有可能在血流中循环更长时间，并有可能被血脑屏障吸收。腔沉淀过程产生超细 NS 颗粒，满足静脉给药的质量要求，并为大脑靶向提供了潜在的解决方案。