Ullmann Kirsten, Leneweit Gero, Nirschl Hermann
Institute of Mechanical Process Engineering and Mechanics, Process Machines, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany.
Carl Gustav Carus-Institute, Association for the Promotion of Cancer Therapy, 75223 Niefern-Oeschelbronn, Germany.
Pharmaceutics. 2021 May 11;13(5):691. doi: 10.3390/pharmaceutics13050691.
This research highlights the capacity of a newly introduced centrifugation process to form liposomes from water-in-fluorocarbon nano-emulsions stabilized with phospholipids to incorporate macromolecular and sensitive active pharmaceutical ingredients (API). The encapsulation efficiency of the produced liposomes, incorporating fluorescein-sodium, bovine serum albumin and fluorecein isothiocyanate dextran as model APIs, is determined by applying Vivaspin centrifugation filtration and quantified by UV-Vis spectroscopy. It was found that higher densities of the fluorocarbons used as the hydrophobic phase enable a higher encapsulation efficiency and that an efficiency of up to 98% is possible depending on the used phospholipid. Among the engineering aspects of the process, a comparison between different membrane substances was performed. Efficiency increases with a higher phospholipid concentration but decreases with the addition of cholesterol. Due to the higher bending modulus, liposome formation is slowed down by cholesterol during liposome closure leading to a greater leakage of the model API. The encapsulation of bovine serum albumin and dextran, both investigated under different osmotic conditions, shows that an efflux negatively affects the encapsulation efficiency while an influx increases the stability. Overall, the process shows the potential for a very high encapsulation efficiency for macromolecules and future pharmaceutical applications.
本研究突出了一种新引入的离心过程的能力，该过程能从用磷脂稳定的氟碳包水纳米乳液中形成脂质体，以包封大分子和敏感的活性药物成分（API）。通过应用Vivaspin离心过滤法测定了所制备脂质体（以荧光素钠、牛血清白蛋白和异硫氰酸荧光素葡聚糖作为模型API）的包封效率，并通过紫外可见光谱法进行定量。结果发现，用作疏水相的氟碳密度越高，包封效率越高，根据所用磷脂的不同，包封效率可达98%。在该过程的工程方面，对不同的膜物质进行了比较。随着磷脂浓度的增加，效率提高，但随着胆固醇的添加而降低。由于弯曲模量较高，在脂质体封闭过程中，胆固醇会减缓脂质体的形成，导致模型API的泄漏增加。在不同渗透条件下对牛血清白蛋白和葡聚糖的包封研究表明，流出会对包封效率产生负面影响，而流入则会提高稳定性。总体而言，该过程显示出对大分子具有非常高的包封效率的潜力以及未来在制药领域的应用前景。
