Nielsen Line Hagner, Rades Thomas, Boyd Ben, Boisen Anja
Department of Micro and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Eur J Pharm Biopharm. 2017 Sep;118:13-20. doi: 10.1016/j.ejpb.2016.12.008. Epub 2016 Dec 18.
The purpose of this study was to prepare cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric microcontainers intended as an oral drug delivery system. The cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that cubosomes were formed after hydration of the spray dried precursor powder. The precursor powder had a mean particle size of 1.3±0.1μm, whereas the mean diameter of the dispersed cubosomes was 282±7nm (PDI: 0.18) measured by dynamic light scattering. 8.5±0.3% (w/w) of OVA was present in the cubosome powder and OVA was found released slowly over the first 70h, followed by a more rapid release. Total release of 47.9±2.8% of loaded OVA occurred over 96h in a buffer at pH 6.8. When the powder was filled into microcontainers, and the opening covered with the pH sensitive polymer Eudragit S100, the pH sensitive 'lid' was intact at gastric pH, but release of OVA from the cubosomes and microcontainers occurred at pH 6.8, releasing 44.1±5.6% of the OVA in 96h. Small-angle X-ray scattering (SAXS) revealed that the 'dry' particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after hydration in buffer at pH 6.8, the particles formed the hexagonal inverse cubic phases, thereby indicating that cubosomes were formed when released from microcontainers.
本研究的目的是通过喷雾干燥制备包封模型抗原卵清蛋白（OVA）的立方液晶纳米粒，并对其进行表征，以期其在口服疫苗递送方面的潜在应用。此外，将立方液晶纳米粒制剂装入用作口服给药系统的聚合物微容器中。立方液晶纳米粒由含有OVA的商用单油酸甘油酯（商品名：Dimodan®）组成，并被通过喷雾干燥制备的葡聚糖壳所包围。冷冻透射电子显微镜用于确认喷雾干燥的前体粉末水合后形成了立方液晶纳米粒。前体粉末的平均粒径为1.3±0.1μm，而通过动态光散射测量的分散立方液晶纳米粒的平均直径为282±7nm（多分散指数：0.18）。立方液晶纳米粒粉末中存在8.5±0.3%（w/w）的OVA，并且发现OVA在最初70小时内缓慢释放，随后释放速度加快。在pH 6.8的缓冲液中，96小时内负载的OVA总释放量为47.9±2.8%。当将粉末装入微容器中，并用pH敏感聚合物Eudragit S100覆盖开口时，pH敏感的“盖子”在胃pH值下保持完整，但OVA从立方液晶纳米粒和微容器中的释放在pH 6.8时发生，96小时内释放了44.1±5.6%的OVA。小角X射线散射（SAXS）表明，“干燥”颗粒由于少量残留水而具有内部有序的脂质结构（层状和反胶束相），并且在pH 6.8的缓冲液中水合后，颗粒形成六方反立方相，从而表明立方液晶纳米粒从微容器中释放时形成。
