School of Pharmacy, University College Cork, Cavanagh Pharmacy Building, Cork, Ireland.
Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Eur J Pharm Sci. 2019 May 15;133:190-204. doi: 10.1016/j.ejps.2019.03.027. Epub 2019 Apr 1.
Gene therapy with RNA and pDNA-based drugs is limited by poor enzymatic stability and poor cellular permeation. The delivery of nucleic acids, in particular by the oral route, remains a major hurdle. This review will focus on the barriers to the oral delivery of nucleic acids and the strategies, in particular formulation strategies, which have been developed to overcome these barriers. Due to their very low oral bioavailability, the most obvious and most investigated biomedical applications for their oral delivery are related to the local treatment of inflammatory bowel diseases and colorectal cancers. Preclinical data but not yet clinical studies support the potential use of the oral route for the local delivery of formulated nucleic acid-based drugs.
基因治疗中的 RNA 和基于 pDNA 的药物受到酶稳定性差和细胞通透性差的限制。核酸的递送，特别是通过口服途径，仍然是一个主要的障碍。本综述将重点讨论核酸口服递送的障碍以及为克服这些障碍而开发的策略，特别是制剂策略。由于其口服生物利用度非常低，其口服递送最明显和最受研究的生物医学应用与局部治疗炎症性肠病和结直肠癌有关。虽然还没有临床研究，但临床前数据支持将口服途径用于局部递送制剂化核酸药物。
