The gentle preparation and the functionalization potential of self-emulsifying drug delivery systems (SEDDS) make them an interesting formulation strategy for oral administration of peptide and protein (p/p) drugs. A series of Kolliphor® RH40 (RH40) and Labrasol® (LAB)-based SEDDS containing either long-chain (LC) or medium-chain (MC) glycerides were formulated and characterized with regard to their rheological behavior, as well as the size distribution and zeta potential of the generated emulsions. Insulin, in order to be incorporated in SEDDS, was complexed with soybean phosphatidylcholine. The ability of different SEDDS to protect the incorporated insulin against enzymatic hydrolysis was evaluated by an in vitro model simulating the intestinal proteolysis. SEDDS were incubated in simulated intestinal fluids in the presence of α-Chymotrypsin (α-CT), and HPLC was used to quantify the remaining insulin. Principal component analysis (PCA) was applied to identify the relations between different excipients and properties of SEDDS that describe the SEDDS protective effect on insulin during in vitro proteolysis. The RH40-SEDDS behaved Newtonian in the presence of ethanol (EtOH) and non-Newtonian in the absence of EtOH, which generated emulsion with droplets between 30 to 300 nm. The LAB-SEDDS always behaved Newtonian and generated polydisperse emulsions with broad size distribution (190-4000 nm). During the in vitro proteolysis, insulin can be effectively protected against α-CT (> 60% remaining insulin after 60 min in vitro proteolysis). According to PCA analysis, insulin was better protected in MC-SEDDS compared to LC-SEDDS, and better in LAB-SEDDS compared to RH40-SEDDS. Monoacyl phosphatidylcholine and Capmul® MCM C8 were recognized as excipients favored for SEDDS protection on insulin. However, SEDDS viscosity and the addition of EtOH in SEDDS played insignificant roles on the remaining insulin after in vitro proteolysis. In summary, an in vitro proteolysis model with increased physiological relevance was applied to enable the optimal design of SEDDS for oral p/p drug delivery.

中文翻译：

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使用模拟肠道蛋白水解的体外模型评估口服胰岛素递送的自乳化药物递送系统。

自乳化药物递送系统（SEDDS）的温和制备和功能化潜力使其成为口服肽和蛋白质（p / p）药物的有趣制剂策略。配制了一系列基于Kolliphor®RH40（RH40）和Labrasol®（LAB）的SEDDS，其中包含长链（LC）或中链（MC）甘油酯，并对其流变行为以及尺寸进行了表征生成的乳液的分布和ζ电位。为了将其掺入SEDDS中，将其与大豆磷脂酰胆碱复合。通过模拟肠道蛋白水解的体外模型评估了不同SEDDS保护掺入的胰岛素抵抗酶水解的能力。将SEDDS在存在α-胰凝乳蛋白酶（α-CT）的模拟肠液中孵育，并用HPLC定量剩余的胰岛素。应用主成分分析（PCA）来鉴定不同辅料与SEDDS性质之间的关系，这些关系描述了SEDDS在体外蛋白水解过程中对胰岛素的保护作用。RH40-SEDDS在存在乙醇（EtOH）的情况下表现为牛顿，而在不存在EtOH的情况下表现为非牛顿，这会​​产生液滴在30至300 nm之间的乳液。LAB-SEDDS始终表现出牛顿性并生成具有宽尺寸分布（190-4000 nm）的多分散乳液。在体外蛋白水解过程中，可以有效地保护胰岛素抵抗α-CT（体外蛋白水解60分钟后> 60％的剩余胰岛素）。根据PCA分析，与LC-SEDDS相比，MC-SEDDS中的胰岛素得到更好的保护，与RH40-SEDDS相比，LAB-SEDDS中的胰岛素得到更好的保护。单酰基磷脂酰胆碱和Capmul®MCM C8被认为是受SEDDS胰岛素保护的辅料。然而，在体外蛋白水解后，SEDDS粘度和在SEDDS中添加EtOH对剩余胰岛素的作用不明显。总之，应用了具有更高生理相关性的体外蛋白水解模型，以实现口服P / P药物递送的SEDDS的最佳设计。