Liau Jin Jau, Hook Sarah, Prestidge Clive A, Barnes Timothy J
School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia.
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Eur J Pharm Biopharm. 2015 Nov;97(Pt A):15-21. doi: 10.1016/j.ejpb.2015.09.018. Epub 2015 Oct 9.
The gastric mucosa provides the entry point for the majority of pathogens, as well as being the induction site for protective immunity; however, there remain few examples of oral vaccines due to the challenges presented by the gastrointestinal route. In this study, we develop a lipid-based multi-compartmental system for oral vaccine delivery. Specifically, we have optimised the formulation of a water-in-oil-in-water double emulsion prepared from a triglyceride - soya bean oil, using surfactants Span 80/Tween 80 and Pluronic F127 to stabilise the internal and external water phases, respectively. Into the internal water phase, we also incorporated a PEGylated liposome, prepared using hydrogenated phosphatidyl choline as a carrier for our model protein, FITC-labelled ovalbumin. We demonstrated the successful incorporation of intact liposomes into the internal water phase of the double emulsion using imaging techniques including cryo-SEM and confocal microscopy. Finally, we use in vitro release studies of FITC-ovalbumin, to provide further confirmation of the multi-compartmental structure of the double emulsion system and demonstrate significant extended release of the entrapped model antigen compared with PEG-liposomes; these characteristics are attractive for oral vaccine delivery.
胃黏膜是大多数病原体的侵入点，也是保护性免疫的诱导部位；然而，由于胃肠道途径带来的挑战，口服疫苗的例子仍然很少。在本研究中，我们开发了一种基于脂质的多室系统用于口服疫苗递送。具体而言，我们优化了由甘油三酯——大豆油制备的水包油包水型双重乳液的配方，使用表面活性剂司盘80/吐温80和普朗尼克F127分别稳定内部和外部水相。在内部水相中，我们还加入了聚乙二醇化脂质体，该脂质体使用氢化磷脂酰胆碱作为我们的模型蛋白——异硫氰酸荧光素标记的卵清蛋白的载体。我们使用包括冷冻扫描电子显微镜和共聚焦显微镜在内的成像技术，证明了完整的脂质体成功地掺入到双重乳液的内部水相中。最后，我们对异硫氰酸荧光素标记的卵清蛋白进行体外释放研究，以进一步证实双重乳液系统的多室结构，并证明与聚乙二醇脂质体相比，包封的模型抗原具有显著的缓释效果；这些特性对于口服疫苗递送具有吸引力。
