Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Thiomatrix Forschungs- und Beratungs GmbH, Trientlgasse 65, 6020 Innsbruck, Austria.
ACS Biomater Sci Eng. 2023 Dec 11;9(12):6797-6804. doi: 10.1021/acsbiomaterials.3c01207. Epub 2023 Nov 23.
Nanoemulsions can be tuned toward enhanced gastro-intestinal retention time by incorporating thiolated surfactants into their surface. Tailoring the chemical reactivity of the thiol headgroup has major influence on mucoadhesive features of the nanoemulsion. Two generations of thiolated surfactants were synthetically derived from PEG-40-stearate featuring either a free thiol group or an S-protected thiol group. The surfactants were characterized regarding critical micelle concentration (CMC), hemolytic activity, and cytotoxicity. Subsequently, they were incorporated into nanoemulsions and the resulting nanoemulsions were characterized regarding particle size, polydispersity index (PDI), zeta potential, and time-dependent stability. Afterward, mucosal interactions as well as mucoadhesion on porcine intestinal mucosa were investigated. Successful synthesis of Cysteine-PEG-40-stearate (CYS-PEG-40-stearate) and MNA-Cysteine-PEG-40-stearate (MNA-CYS-PEG-40-stearate) was confirmed by H NMR spectroscopy. Both chemical modifications led to slightly elevated CMC values while preserving low cytotoxicity and hemotoxicity. Incorporation into nanoemulsions had minor influence on overall physical particle characteristics, while interactions with mucus and mucoadhesiveness of the nanoemulsions were drastically improved resulting in the rank order PEG-40-stearate < CYS-PEG-40-stearate < MNA-CYS-PEG-40-stearate. Accordingly, thiolated surfactants, especially S-protected derivatives, are versatile tools to generate highly mucoadhesive nanoemulsions.
纳米乳可以通过在其表面加入巯基化表面活性剂来调节其在胃肠道中的滞留时间。修饰硫醇基团的化学反应性对纳米乳的粘膜粘附特性有很大影响。两种巯基化表面活性剂是从 PEG-40-硬脂酸酯合成得到的，具有游离硫醇基团或 S 保护的硫醇基团。对表面活性剂的临界胶束浓度 (CMC)、溶血活性和细胞毒性进行了表征。然后将其掺入纳米乳液中，并对所得纳米乳液的粒径、多分散指数 (PDI)、zeta 电位和时变稳定性进行了表征。之后，研究了粘膜相互作用以及在猪肠粘膜上的粘膜粘附。通过 1 H NMR 光谱证实了半胱氨酸-PEG-40-硬脂酸酯 (CYS-PEG-40-硬脂酸酯) 和 MNA-半胱氨酸-PEG-40-硬脂酸酯 (MNA-CYS-PEG-40-硬脂酸酯) 的成功合成。两种化学修饰都导致 CMC 值略有升高，但仍保持低细胞毒性和低溶血毒性。掺入纳米乳液对整体物理颗粒特性的影响较小，而纳米乳液与粘液的相互作用和粘膜粘附性得到了显著改善，结果为 PEG-40-硬脂酸酯 < CYS-PEG-40-硬脂酸酯 < MNA-CYS-PEG-40-硬脂酸酯。因此，巯基化表面活性剂，特别是 S 保护衍生物，是生成高度粘膜粘附性纳米乳液的多功能工具。
