Controlled-release drug delivery systems prodrug

When the transdermal penetration of a drug is inadequate to achieve and maintain a plasma concentration above the minimum therapeutic concentration required to produce the desired effect, a lipophilic prodrug that will be metabolized in the epidermis to the active drug could be used in the development of a controlled-release transdermal delivery system. This approach has been applied to estradiol esters (diacetate and valerate) which are rapidly converted by esterases in the skin tissue to estradiol (Chien et al, 1985). The prodrug serves to increase the transdermal bioavailability of the active drug to which it is converted by metabolism (generally ester hydrolysis) during the percutaneous absorption process. 

Y. H. Choe, C. D. Conover, D. C. Wu, M. Royzen, Y. Gervacio, V. Borowski, M. Mehlig and R. B. Greenwald, Anticancer drug delivery systems Multi-loaded N-4-acyl poly(ethylene glycol) prodrugs of ara-C. II. Efficacy in ascites and solid tumors, /. Control Release, 79, 55-70 (2002). 

---