title: Dermal and transdermal delivery: prodrugs.
abstract: Attempts to deliver drugs into and through the skin (dermal and transdermal delivery) have not been very successful because the physicochemical properties of drugs are often not optimal. Prodrugs can be used to optimize those physicochemical properties of drugs and optimize their delivery by transiently masking their polar functional groups. For a drug to cross the rate-limiting barrier to delivery (the stratum corneum) it must dissolve in and cross multiple lipid and aqueous phases within the stratum corneum. Prodrugs can be designed to exhibit increased lipid and aqueous solubilities resulting in increased delivery. In order to identify the optimal prodrugs, they must be evaluated as saturated solutions where their thermodynamic activities are maximal in the solution and in the skin. If prodrugs are evaluated at concentrations less than at saturation, inaccurate conclusions about the optimal physicochemical properties may result. Prodrugs must be designed to optimize both their lipid and aqueous solubilities to optimize their delivery into and through the skin.
authors: Department of Medicinal Chemistry, University of Florida, PO Box 100485, Gainesville, Fl 32610, USA. sloan@cop.ufl.edu
authors: Kenneth B
authors: KB
authors: Sloan
authors: Hemamalini
authors: H
authors: Devarajan-Ketha
authors: Scott C
authors: SC
authors: Wasdo
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D006801:Humans; D011355:Prodrugs / Q000008:administration & dosage*; D012867:Skin / Q000378:metabolism*; D012995:Solubility; D013816:Thermodynamics
chemical_list: D011355:Prodrugs