Schreiner Jonas, Brettner Felix E B, Gier Stefanie, Vogel-Kindgen Sarah, Windbergs Maike
Institute of Pharmaceutical Technology, Goethe-University Frankfurt, 60438 Frankfurt am Main, Germany.
Institute of Pharmaceutical Technology, Goethe-University Frankfurt, 60438 Frankfurt am Main, Germany.
Eur J Pharm Biopharm. 2024 Sep;202:114408. doi: 10.1016/j.ejpb.2024.114408. Epub 2024 Jul 14.
The therapeutic effects of orally administered nanocarriers depend on their ability to effectively permeate the intestinal mucosa, which is one of the major challenges in oral drug delivery. Microfold cells are specialized enterocytes in the intestinal epithelium known for their high transcytosis abilities. This study aimed to compare and evaluate two targeting approaches using surface modifications of polymer-based nanocarriers, whereas one generally addresses enterocytes, and one is directed explicitly to microfold cells via targeting the sialyl Lewis motif on their surface. We characterized the resulting carriers in terms of size and charge, supplemented by scanning electron microscopy to confirm their structural properties. For predictive biological testing and to assess the intended targeting effect, we implemented two human intestinal in vitro models containing microfold-like cells. Both models were thoroughly characterized prior to permeation studies with the different nanocarriers. Our results demonstrated improved transport for both targeted formulations compared to undecorated carriers in the in vitro models. Notably, there was an enhanced uptake in the presence of microfold-like cells, particularly for the nanocarriers directed by the anti-sialyl Lewis antibody. These findings highlight the potential of microfold cell targeting to improve oral administration of drugs and emphasize the importance of using suitable and well-characterized in vitro models for testing novel drug delivery strategies.
口服纳米载体的治疗效果取决于它们有效渗透肠黏膜的能力，而这是口服药物递送中的主要挑战之一。微褶细胞是肠上皮中的特化肠细胞，以其高转胞吞能力而闻名。本研究旨在比较和评估两种使用基于聚合物的纳米载体表面修饰的靶向方法，其中一种通常针对肠细胞，另一种则通过靶向微褶细胞表面的唾液酸化路易斯基序明确地指向微褶细胞。我们从尺寸和电荷方面对所得载体进行了表征，并辅以扫描电子显微镜来确认其结构特性。为了进行预测性生物学测试并评估预期的靶向效果，我们建立了两种含微褶样细胞的人肠道体外模型。在使用不同纳米载体进行渗透研究之前，对这两种模型都进行了全面表征。我们的结果表明，在体外模型中，与未修饰的载体相比，两种靶向制剂的转运都有所改善。值得注意的是，在存在微褶样细胞的情况下摄取有所增加，特别是对于由抗唾液酸化路易斯抗体引导的纳米载体。这些发现突出了微褶细胞靶向在改善药物口服给药方面的潜力，并强调了使用合适且表征良好的体外模型来测试新型药物递送策略的重要性。
