Jiang Xiaohe, Wang Ning, Liu Chang, Zhuo Yan, Liang Li, Gan Yong, Yu Miaorong
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330000, China.
Drug Discov Today. 2023 Apr;28(4):103507. doi: 10.1016/j.drudis.2023.103507. Epub 2023 Jan 21.
In recent decades, advances in chemical synthesis and delivery systems have accelerated the development of therapeutic nucleic acids, several of which have been approved by the Us Food and Drug Administration (FDA). Oral nucleic acid delivery is preferred because of its simplicity and patient compliance, but it still presents distinct challenges. The negative charge, hydrophilicity, and large molecular weight of nucleic acids combined with in vivo gastrointestinal (GI) barriers (e.g., acidic pH, enzymes, mucus, and intestinal epithelial cells) severely hinder their delivery efficacy. Recently, various nanoparticles (NPs), ranging from polymeric to lipid-based (L)NPs and extracellular vesicles (EVs), have been extensively explored to address these obstacles. In this review, we describe the physiological barriers in the GI tract and summarize recent advances in NP-based oral nucleic acid therapeutics.
近几十年来，化学合成和递送系统的进步加速了治疗性核酸的发展，其中几种已被美国食品药品监督管理局（FDA）批准。口服核酸递送因其简便性和患者依从性而更受青睐，但仍面临独特的挑战。核酸的负电荷、亲水性和大分子质量，再加上体内胃肠道（GI）屏障（如酸性pH值、酶、黏液和肠上皮细胞），严重阻碍了它们的递送效果。最近，人们广泛探索了各种纳米颗粒（NPs），从聚合物纳米颗粒到基于脂质的（L）NPs和细胞外囊泡（EVs），以克服这些障碍。在这篇综述中，我们描述了胃肠道中的生理屏障，并总结了基于纳米颗粒的口服核酸治疗的最新进展。
