RISE Research Institutes of Sweden, Drottning Kristinas väg 45, Box 5607 Stockholm SE-11486, Sweden; Department of Chemistry and Chemical Engineering, Applied Chemistry, Chalmers University of Technology, Kemigården 4, Göteborg SE-41296, Sweden.
RISE Research Institutes of Sweden, Drottning Kristinas väg 45, Box 5607 Stockholm SE-11486, Sweden.
J Colloid Interface Sci. 2018 Jul 15;522:126-135. doi: 10.1016/j.jcis.2018.03.062. Epub 2018 Mar 20.
Liquid crystalline nanoparticles (LCNPs), e.g. cubosomes and hexosomes, are receiving more and more attraction as drug delivery vehicles. Dry powder formulation that forms LCNPs upon hydration can be advantageous to make new routes of administration accessible. In this work, we investigate use of three disaccharides (lactose, trehalose and sucrose) as protective matrices for glycerol monooleate based LCNP forming powders produced by freeze-drying. Phase behavior, particle size and size distributions at the different preparation steps were monitored by small angle x-ray scattering (SAXS) and dynamic light scattering (DLS). Particle appearance was imaged by cryogenic transmission electron microscopy (cryo-TEM). Moreover, the therapeutic relevant antimicrobial peptide AP114 (plectasin derivative) was incorporated in the formulations. Peptide encapsulation and release as well as in vitro antibacterial effect were investigated. Results showed that all freeze-dried powders did form particles with liquid crystalline structure upon hydration. However, a phase transition from the bicontinuous cubic Pn3m to the reversed hexagonal was observed, as a consequence of sugar addition and the freeze-drying procedure. Data indicates that trehalose is the preferred choice of lyo-protectant in order to maintain a mono-modal particle size distribution. In addition, antimicrobial activity of AP114-containing formulations was found to be highest for the formulation containing trehalose. The release kinetics of AP114 from the nanoparticles was strongly affected by the dimensions of the hexagonal phase. Larger dimension of the hexagonal phase, significantly improved the release of AP114 and antimicrobial activity of the formulation.
液晶纳米颗粒（LCNPs），例如立方纳米囊泡和六方纳米囊泡，作为药物递送载体越来越受到关注。形成 LCNPs 的干粉制剂在水合时可以使新的给药途径变得可行。在这项工作中，我们研究了三种二糖（乳糖、海藻糖和蔗糖）作为甘油单油酸酯基 LCNP 形成粉末的保护性基质的用途，这些粉末是通过冷冻干燥制备的。通过小角 X 射线散射（SAXS）和动态光散射（DLS）监测不同制备步骤的相行为、粒径和粒径分布。通过低温透射电子显微镜（cryo-TEM）对颗粒外观进行成像。此外，还将治疗相关的抗菌肽 AP114（plectasin 衍生物）掺入制剂中。研究了肽的包封和释放以及体外抗菌效果。结果表明，所有冷冻干燥的粉末在水合时都会形成具有液晶结构的颗粒。然而，由于添加了糖和冷冻干燥过程，观察到从双连续立方 Pn3m 到反向六方的相转变。数据表明，为了保持单峰粒径分布，海藻糖是首选的冻干保护剂。此外，含有 AP114 的制剂的抗菌活性以含有海藻糖的制剂最高。AP114 从纳米颗粒中的释放动力学受到六方相尺寸的强烈影响。较大的六方相尺寸显著改善了 AP114 的释放和制剂的抗菌活性。
