Polyethylene glycol (PEG) and its derivatives are widely used in delivery systems to protect bioactive peptides and proteins against premature degradation. In this study, we sought to understand whether or not bioactive proteins at the interface of emulsions can be protected by PEG chains during in vitro gastrointestinal digestion. We designed an emulsion stabilised by both PEG 40 stearate (PEG 40 St) and a bioactive protein, bovine lactoferrin (LF), and we monitored the fate of LF during in vitro digestion. The PEG–LF emulsions displayed a droplet diameter of 200 nm and remained colloidally and morphologically stable for at least 2 h in the simulated gastric fluid; in contrast, the control emulsions with LF alone showed droplet flocculation. After 2 h of gastric digestion, the LF in these emulsions was largely protected (84% remaining), whereas only 23% LF remained in the control emulsions. This protective effect on LF might be related to an inhibition of pepsin activity by PEG 40 St, independent of the location of the LF. Under intestinal conditions, the PEG–LF emulsions had good stability and slower lipolysis than the control emulsions, but LF was prone to immediate degradation within 5 min, regardless of the protection from PEG 40 St, suggesting that PEG 40 St had no inhibitory effect on pancreatic proteases. Overall, this work shows promise for using PEG 40 St, a food-grade emulsifier, to prevent premature gastric digestion of bioactive proteins following oral delivery.

Graphical Abstract

聚乙二醇（PEG）及其衍生物广泛用于输送系统中，以保护生物活性肽和蛋白质免于过早降解。在这项研究中，我们试图了解在体外胃肠消化过程中，乳剂界面上的生物活性蛋白是否可以被PEG链保护。我们设计了一种由PEG 40硬脂酸酯（PEG 40 St）和生物活性蛋白牛乳铁蛋白（LF）稳定的乳液，并在体外消化过程中监测了LF的命运。PEG-LF乳剂的液滴直径为200 nm，在模拟胃液中至少2 h保持胶体和形态稳定。相反，仅含LF的对照乳液显示出液滴絮凝。胃消化2小时后，这些乳剂中的LF得到了很大程度的保护（剩余84％），而对照乳液中仅剩余23％的LF。对LF的这种保护作用可能与PEG 40 St对胃蛋白酶活性的抑制有关，而与LF的位置无关。在肠道条件下，PEG-LF乳剂比对照乳剂具有良好的稳定性和较慢的脂解作用，但是LF易于在5分钟内降解，而不受PEG 40 St的保护，这表明PEG 40 St对乳胶没有抑制作用。胰腺蛋白酶。总的来说，这项工作显示出使用食品级乳化剂PEG 40 St预防口服递送后胃中生物活性蛋白过早消化的希望。PEG-LF乳剂比对照乳剂具有良好的稳定性和较慢的脂解作用，但是LF易于在5分钟内降解，而不受PEG 40 St的保护，这表明PEG 40 St对胰腺蛋白酶没有抑制作用。总的来说，这项工作显示出使用食品级乳化剂PEG 40 St预防口服递送后胃中生物活性蛋白过早消化的希望。PEG-LF乳剂比对照乳剂具有良好的稳定性和较慢的脂解作用，但是LF易于在5分钟内降解，而不受PEG 40 St的保护，这表明PEG 40 St对胰腺蛋白酶没有抑制作用。总的来说，这项工作显示出使用食品级乳化剂PEG 40 St预防口服递送后胃中生物活性蛋白过早消化的希望。

图形概要