Strachan Jamie B, Dyett Brendan P, Jones Nykola C, Hoffmann Søren Vrønning, Valery Celine, Conn Charlotte E
School of Science, STEM College, RMIT University, Melbourne 3000, Australia.
ISA, Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C, Denmark.
J Colloid Interface Sci. 2021 Jun 15;592:135-144. doi: 10.1016/j.jcis.2021.02.027. Epub 2021 Feb 18.
Oral delivery of the protein drug insulin is not currently possible due to rapid degradation of the secondary structure in low pH conditions in the stomach and under the influence of digestive enzymes in the gastrointestinal tract. Effective oral delivery of insulin and other protein- or peptide-based drugs will, therefore, require encapsulation in a material or nanoparticle. Herein we investigate the ability of the lipid bicontinuous cubic phase formed by two lipids, monoolein (MO) and phytantriol (PT), to protect encapsulated insulin from degradation by the enzyme chymotrypsin, typically found in the small intestine. High encapsulation efficiency (>80%) was achieved in both lipid cubic phases with retention of the underlying cubic nanostructure. Release of insulin from the cubic matrix was shown to be diffusion-controlled; the release rate was dependent on the cubic nanostructure and consistent with measured diffusion coefficients for encapsulated insulin. Encapsulation was shown to significantly retard enzymatic degradation relative to that in water, with the protective effect lasting up to 2 h, exemplifying the potential of these materials to protect the encapsulated protein payload during oral delivery.
由于胃中低pH条件下二级结构的快速降解以及胃肠道中消化酶的影响，目前蛋白质药物胰岛素无法通过口服给药。因此，胰岛素和其他基于蛋白质或肽的药物的有效口服给药需要封装在一种材料或纳米颗粒中。在此，我们研究了由单油酸甘油酯（MO）和植烷三醇（PT）两种脂质形成的脂质双连续立方相保护包封的胰岛素免受胰凝乳蛋白酶（通常存在于小肠中）降解的能力。在两种脂质立方相中均实现了高封装效率（>80%），同时保留了底层的立方纳米结构。胰岛素从立方基质中的释放显示为扩散控制；释放速率取决于立方纳米结构，并且与测得的包封胰岛素的扩散系数一致。相对于水中的情况，封装显示出显著延缓酶降解的作用，保护作用可持续长达2小时，例证了这些材料在口服给药过程中保护包封的蛋白质有效载荷的潜力。
