A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove #06-06 Immunos, Singapore 138648, Singapore.
Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore (NUS), 4 Science Drive 2, Singapore 117544, Singapore.
Int J Pharm. 2024 Aug 15;661:124435. doi: 10.1016/j.ijpharm.2024.124435. Epub 2024 Jul 8.
RNA therapeutics represent a rapidly expanding platform with game-changing prospects in personalized medicine. The disruptive potential of this technology will overhaul the standard of care with reference to both primary and specialty care. To date, RNA therapeutics have mostly been delivered parenterally via injection, but topical administration followed by intradermal or transdermal delivery represents an attractive method that is convenient to patients and minimally invasive. The skin barrier, particularly the lipid-rich stratum corneum, presents a significant hurdle to the uptake of large, charged oligonucleotide drugs. Therapeutic oligonucleotides need to be engineered for stability and specificity and formulated with state-of-the-art delivery strategies for efficient uptake. This review will cover various passive and active strategies deployed to enhance permeation through the stratum corneum and achieve effective delivery of RNA therapeutics to treat both local skin disorders and systemic diseases. Some strategies to achieve selectivity between local and systemic administration will also be discussed.
RNA 疗法是一个快速发展的平台，在个性化医疗方面具有改变游戏规则的前景。这项技术的颠覆性潜力将彻底改变初级和专科护理的标准。迄今为止，RNA 疗法主要通过注射进行肠胃外给药，但局部给药后通过皮内或透皮给药是一种有吸引力的方法，对患者来说方便且微创。皮肤屏障，特别是富含脂质的角质层，是大型带电荷的寡核苷酸药物吸收的一个重大障碍。治疗性寡核苷酸需要进行稳定性和特异性设计，并采用最先进的给药策略以实现有效吸收。本综述将涵盖各种被动和主动策略，以增强穿过角质层的渗透，实现 RNA 疗法的有效递送，以治疗局部皮肤疾病和系统性疾病。还将讨论一些在局部和全身给药之间实现选择性的策略。
