Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel.
Molecules. 2024 Aug 19;29(16):3909. doi: 10.3390/molecules29163909.
Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) is a well-known penetration enhancer widely used in commercial applications. This study aims to broaden its properties through a novel strategy of converting it into its phenolate salts. The objective is to investigate the synthesis of SNAC phenolate salts, specifically SNAC-choline (SNAC-CH), SNAC-sodium (SNAC-Na), and SNAC-phosphatidylcholine (SNAC-PC), and to explore their potential application in improving the oral absorption of semaglutide.
The synthesis of SNAC phenolate salts was confirmed through 1H-NMR, FTIR, and an elemental analysis of C, H, N, and O. In vivo testing was conducted to assess the oral delivery of semaglutide using these synthesized SNAC phenolate salts. Pharmacokinetic (PK) values were measured to evaluate the impact on drug absorption.
The synthesis of SNAC phenolate salts (SNAC-CH, SNAC-Na, and SNAC-PC) was successfully achieved under appropriate conditions, and their structures were confirmed using analytical techniques such as IR, NMR, and CHN elemental analysis. The paradigm of their use was evaluated through an oral pharmacokinetic (PK) in vivo study using SNAC phenolate salts, which did not impair the original SNAC PK values. This suggests that this strategy holds promise as a potential new effective enhancer for oral absorption.
The utilization of SNAC phenolate salts presents a novel and promising strategy for extending the verity of penetration enhancers' molecules and properties. Synthesizing phenolate salts represents a new chemical strategy that may open new avenues in molecular development. This approach holds future potential to enhance the oral delivery of peptide drugs like semaglutide without compromising therapeutic efficacy. Overall, it offers significant advancements in the field by providing a potential alternative to injectable peptides through oral delivery systems.
N-[8-(2-羟基苯甲酰基)氨基]辛酸钠（SNAC）是一种广为人知的渗透增强剂，广泛应用于商业用途。本研究旨在通过将其转化为酚盐的新策略来拓宽其性能。目的是合成 SNAC 酚盐，特别是 SNAC-胆碱（SNAC-CH）、SNAC-钠（SNAC-Na）和 SNAC-磷脂酰胆碱（SNAC-PC），并探讨其在改善司美格鲁肽口服吸收方面的潜在应用。
通过 1H-NMR、FTIR 和 C、H、N、O 的元素分析证实 SNAC 酚盐的合成。通过体内试验评估使用这些合成的 SNAC 酚盐对司美格鲁肽的口服递送。测量药代动力学（PK）值以评估对药物吸收的影响。
在适当的条件下成功合成了 SNAC 酚盐（SNAC-CH、SNAC-Na 和 SNAC-PC），并通过 IR、NMR 和 CHN 元素分析等分析技术确认了它们的结构。通过使用 SNAC 酚盐进行体内口服药代动力学（PK）研究评估了它们的使用范例，这并没有损害原始 SNAC PK 值。这表明该策略有希望成为口服吸收的潜在新有效增强剂。
使用 SNAC 酚盐为扩展渗透增强剂分子和性质的多样性提供了一种新颖而有前途的策略。合成酚盐代表了一种新的化学策略，可能为分子开发开辟新途径。这种方法具有增强像司美格鲁肽这样的肽类药物的口服递送而不影响治疗效果的未来潜力。总的来说，它通过提供一种替代注射肽的口服递送系统，在该领域取得了重大进展。
