Institut de Ciència de Materials de Barcelona (CSIC), Campus Universitari de Bellaterra, Cerdanyola, (Spain).
Biomedical Research Institute Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, Barcelona, (Spain).
Nanomedicine. 2020 Feb;24:102136. doi: 10.1016/j.nano.2019.102136. Epub 2019 Dec 13.
Quatsomes are outstanding new lipid-based nanovesicles that are highly homogeneous and stable in different media for years, but the composition must be carefully chosen to avoid any potentially toxic side effects in in vivo applications. To this end, we have developed and studied a novel type of Quatsomes composed of cholesterol and myristalkonium chloride (MKC), the latter being extensively used as antimicrobial preservative in many ophthalmic and parenteral formulations on the EU and USA market. We have synthesized these novel MKC-Quatsomes in different media that are suitable for parenteral administration, and confirmed their stability in these media for 18 months, as well as the stability in human serum for 24 hours. Biodistribution assays were performed after intravenous injection of fluorescently labeled MKC-Quatsomes in live mice bearing xenografted colorectal tumors, showing nanovesicle accumulation in tumors, liver, spleen, and kidneys. No histological alteration or toxicity was observed in any of these organs.
Quatsomes 是一种新型的基于脂质的纳米囊泡，具有高度的均一性和稳定性，可以在不同的介质中稳定存在多年，但为了避免在体内应用中产生任何潜在的毒性副作用，其组成必须经过精心选择。为此，我们开发并研究了一种新型的由胆固醇和十四烷铵氯化物 (MKC) 组成的 Quatsomes，后者在欧盟和美国市场上的许多眼科和肠胃外制剂中被广泛用作抗菌防腐剂。我们在适合肠胃外给药的不同介质中合成了这些新型的 MKC-Quatsomes，并确认了它们在这些介质中 18 个月的稳定性，以及在人血清中 24 小时的稳定性。在携带异种移植结直肠肿瘤的活小鼠中静脉注射荧光标记的 MKC-Quatsomes 后进行了生物分布测定，结果显示纳米囊泡在肿瘤、肝脏、脾脏和肾脏中积累。在这些器官中均未观察到组织学改变或毒性。
