Cholakova Diana, Glushkova Desislava, Tcholakova Slavka, Denkov Nikolai
Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, 1 James Bourchier Avenue, 1164 Sofia, Bulgaria.
ACS Nano. 2020 Jul 28;14(7):8594-8604. doi: 10.1021/acsnano.0c02946. Epub 2020 Jul 1.
We describe several unexpected phenomena, caused by a solid-solid phase transition (gel-to-crystal) typical for all main classes of lipid substances: phospholipids, triglycerides, diglycerides, alkanes, . We discovered that this transition leads to spontaneous formation of a network of nanopores, spreading across the entire lipid structure. These nanopores are spontaneously impregnated (flooded) by water when appropriate surfactants are present, thus fracturing the lipid structure at a nanoscale. As a result, spontaneous disintegration of the lipid into nanoparticles or formation of double emulsions is observed, just by cooling and heating of an initial coarse lipid-in-water dispersion around the lipid melting temperature. The process of nanoparticle formation is effective even after incorporation of medical drugs of high load, up to 50% in the lipid phase. The role of the main governing factors is clarified, the procedure is optimized, and the possibility for its scaling-up to industrially relevant amounts is demonstrated.
我们描述了由所有主要类别的脂质物质(磷脂、甘油三酯、甘油二酯、烷烃等)典型的固-固相变(凝胶-晶体)引起的几种意外现象。我们发现这种转变会导致纳米孔网络的自发形成,该网络遍布整个脂质结构。当存在适当的表面活性剂时,这些纳米孔会被水自发填充(淹没),从而在纳米尺度上破坏脂质结构。结果,仅通过在脂质熔点附近对初始粗水包脂质分散体进行冷却和加热,就可以观察到脂质自发分解成纳米颗粒或形成双重乳液。即使在掺入高达脂质相50%的高负载药物后,纳米颗粒形成过程仍然有效。阐明了主要控制因素的作用,优化了该过程,并证明了将其扩大到工业相关量的可能性。