Rautio Jarkko, Laine Krista, Gynther Mikko, Savolainen Jouko
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211, Kuopio, Finland.
AAPS J. 2008;10(1):92-102. doi: 10.1208/s12248-008-9009-8. Epub 2008 Feb 5.
Central nervous system (CNS) drug delivery remains a major challenge, despite extensive efforts that have been made to develop novel strategies to overcome obstacles. Prodrugs are bioreversible derivatives of drug molecules that must undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which subsequently exerts the desired pharmacological effect. In both drug discovery and drug development, prodrugs have become an established tool for improving physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically active agents that overcome barriers to a drug's usefulness. This review provides insight into various prodrug strategies explored to date for CNS drug delivery, including lipophilic prodrugs, carrier- and receptor-mediated prodrug delivery systems, and gene-directed enzyme prodrug therapy.
尽管人们为开发克服障碍的新策略付出了巨大努力，但中枢神经系统（CNS）药物递送仍然是一个重大挑战。前药是药物分子的生物可逆衍生物，必须在体内经历酶促和/或化学转化才能释放出活性母体药物，随后发挥所需的药理作用。在药物发现和药物开发中，前药已成为一种既定工具，用于改善药理活性剂的物理化学、生物药剂学或药代动力学性质，克服药物应用的障碍。本综述深入探讨了迄今为止为中枢神经系统药物递送探索的各种前药策略，包括亲脂性前药、载体和受体介导的前药递送系统以及基因导向酶前药疗法。
