progress in drug delivery to the central nervous system by the prodrug approach进展的中枢神经系统药前体药物的方法.pdfVIP

Molecules 2008, 13, 1035-1065; DOI: 10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /molecules Review Progress in Drug Delivery to the Central Nervous System by the Prodrug Approach Barbara Pavan 1,*, Alessandro Dalpiaz 2, Nunzia Ciliberti 2, Carla Biondi 1, Stefano Manfredini 2 2 and Silvia Vertuani 1 University of Ferrara, Department of Biology, General Physiology Section, via L. Borsari 46, 44100, Ferrara, Italy 2 University of Ferrara, Department of Pharmaceutical Sciences, via Fossato di Mortara 19, 44100, Ferrara, Italy * Author to whom correspondence should be addressed; E-mail: barbara.pavan@unife.it; Tel.: +39- 0532-455476; Fax: +39-0532-207143 Received: 1 February 2008; in revised form: 1 April 2008 / Accepted: 30 April 2008 / Published: 1 May 2008 Abstract: This review describes specific strategies for targeting to the central nervous system (CNS). Systemically administered drugs can reach the brain by crossing one of two physiological barriers resistant to free diffusion of most molecules from blood to CNS: the endothelial blood-brain barrier or the epithelial blood-cerebrospinal fluid barrier. These tissues constitute both transport and enzymatic barriers. The most common strategy for designing effective prodrugs relies on the increase of parent drug lipophilicity. However, increasing lipophilicity without a concomitant increase in rate and selectivity of prodrug bioconversion in the brain w