Karamanidou Theodora, Karidi Konstantina, Bourganis Vassilis, Kontonikola Katerina, Kammona Olga, Kiparissides Costas
Department of Chemical Engineering, Aristotle University of Thessaloniki, P.O. Box 472, 54124 Thessaloniki, Greece.
Chemical Process & Energy Resources Research Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
Eur J Pharm Biopharm. 2015 Nov;97(Pt A):223-9. doi: 10.1016/j.ejpb.2015.04.013. Epub 2015 Apr 29.
The development of a novel, mucus permeating SNEDDS formulation for oral insulin delivery containing a hydrophobic ion pair of insulin/dimyristoyl phosphatidylglycerol (INS/DMPG) is presented. Three oil/surfactant/cosurfactant combinations and 27 weight ratios of oil, surfactant and cosurfactant for each combination were evaluated with the aid of ternary phase diagrams, for the incorporation of the protein/phospholipid complex. The developed formulation was characterized by an average droplet diameter of 30-45 nm. Depending on the initial protein concentration, the loading of insulin in SNEDDS varied between 0.27 and 1.13 wt%. The therapeutic protein was found to be efficiently protected from enzymatic degradation by intestinal enzymes (i.e., trypsin, α-chymotrypsin). The SNEDDS formulation exhibited increased mucus permeability and did not appear to be affected by ionic strength. The incorporation of INS/DMPG in SNEDDS prevented an initial burst release of insulin. INS/DMPG loaded SNEDDS were found to be non-cytotoxic up to a concentration of 2mg/ml. According to the reported results, the incorporation of the hydrophobic ion pair of INS/DMPG in SNEDDS could be regarded as a promising strategy for the oral delivery of insulin.
本文介绍了一种新型的、可渗透黏液的自乳化药物传递系统（SNEDDS）制剂，用于口服胰岛素递送，该制剂含有胰岛素/二肉豆蔻酰磷脂酰甘油（INS/DMPG）的疏水离子对。借助三元相图，评估了三种油/表面活性剂/助表面活性剂组合以及每种组合的27种油、表面活性剂和助表面活性剂的重量比，用于包载蛋白质/磷脂复合物。所开发的制剂的特征在于平均液滴直径为30 - 45纳米。根据初始蛋白质浓度，SNEDDS中胰岛素的载量在0.27至1.13 wt%之间变化。发现治疗性蛋白质能有效免受肠道酶（即胰蛋白酶、α-胰凝乳蛋白酶）的酶促降解。SNEDDS制剂表现出增加的黏液渗透性，并且似乎不受离子强度的影响。在SNEDDS中加入INS/DMPG可防止胰岛素的初始突释。发现载有INS/DMPG的SNEDDS在浓度高达2mg/ml时无细胞毒性。根据报道的结果，在SNEDDS中加入INS/DMPG的疏水离子对可被视为口服递送胰岛素的一种有前景的策略。
