Development of bi-polymer lipid hybrid nanocarrier (BLN) to improve the entrapment and stability of insulin for efficient oral delivery
Development of bi-polymer lipid hybrid nanocarrier (BLN) to improve the entrapment and stability of insulin for efficient oral delivery
复制标题
DOI：
10.1016/j.jddst.2019.01.007
复制
发表时间：
2019-02-01
影响因子：
5
通讯作者：
Wong, Ho-Lun
中科院分区：
文献类型：
--
作者：
Boushra, Mariam;Tous, Sozan;Wong, Ho-Lun
固体脂质纳米粒子（SLN）已被证明对于口服蛋白质递送具有良好的特性。然而，由于其疏水性，它们的蛋白质捕获效率 (EE%) 值仍然有限。在这项研究中，我们报告了一种新策略，将两种聚合物赋形剂加入到基于双乳液的 SLN 中，以解决包封效率低下的问题。使用胰岛素作为模型蛋白质药物，对所得混合纳米载体（称为双聚合物脂质纳米载体（BLN））的理化性质、药物和颗粒稳定性、体外生物学行为和体内降血糖作用进行了评估。结果发现，内部水相中含有 PEG 6000 且脂相中含有 PLGA 的 BLN 显示出良好的尺寸（约 240 nm）和相当窄的粒径分布。与标准 w/o/w SLN 相比，双聚合物策略将胰岛素 EE% 提高了 2.5 倍（分别为 50% 和 20%），同时保留了胰岛素的化学稳定性和生物活性。 BLN 在胃肠道条件下表现出良好的分散稳定性，可以很好地保护包埋的胰岛素免受酶促降解，并且可以很好地内化到 Caco-2 细胞中，且细胞毒性最小。 BLN 递送的口服胰岛素的药理学有效性（6.1%）与凝集素修饰的 SLN 相当。总之，BLN 是一种有前景的混合纳米载体设计，可实现高效的口服胰岛素递送。
Solid lipid nanoparticles (SLN) have demonstrated favorable properties for oral protein delivery. However, their protein entrapment efficiency (EE%) values remain limited due to their hydrophobic nature. In this study, we reported a new strategy in which two polymeric excipients were incorporated into the double-emulsion based SLN to address this entrapment inefficiency issue. Using insulin as the model protein drug, the resulting hybrid nanocarriers known as bi-polymer lipid nanocarriers (BLN) were evaluated for physicochemical properties, drug and particle stability, in vitro biological behaviors and in vivo hypoglycemic effect. It was found that BLN containing PEG 6000 in internal aqueous phase and PLGA in lipid phase showed favorable size (around 240 nm) and reasonably narrow particle size distribution. The bi-polymer strategy improved insulin EE% over standard w/o/w SLN by 2.5-fold (similar to 50% versus 20%) while preserving the insulin chemical stability and biological activity. BLN demonstrated good dispersion stability under gastrointestinal conditions, protected the entrapped insulin against enzymatic degradation well, and were well internalized into Caco-2 cells with minimal cytotoxicity. Pharmacological availability of oral insulin delivered by BLN (6.1%) was comparable to lectin-modified SLN. To conclude, BLN is a promising hybrid nanocarrier design to achieve efficient oral insulin delivery.