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Abstract #21571 Published in IGR 10-3
Scope and limitations of the co-drug approach to topical drug delivery
Lau WM; White AW; Gallagher SJ; Donaldson M; McNaughton G; Heard CMCurrent Pharmaceutical Design 2008; 14: 794-802
Many currently available drugs show unfavourable physicochemical properties for delivery into or across the skin and temporary chemical modulation of the penetrant is one option to achieve improved delivery properties. Pro-drugs are chemical derivatives of an active drug which is covalently bonded to an inactive pro-moiety in order to overcome pharmaceutical and pharmacokinetic barriers. A pro-drug relies upon conversion within the body to release the parent active drug (and pro-moiety) to elicit its pharmacological effect. The main drawback of this approach is that the pro-moiety is essentially an unwanted ballast which, when released, can lead to adverse effects. The term 'co-drug' refers to two or more therapeutic compounds active against the same disease bonded via a covalent chemical linkage and it is this approach which is reviewed for the first time in the current article. For topically applied co-drugs, each moiety is liberated in situ, either chemically or enzymatically, once the stratum comeum barrier has been overcome by the co-drug. Advantages include synergistic modulation of the disease process, enhancement of drug delivery and pharmacokinetic properties and the potential to enhance stabilithy by masking of labile functional groups. The amount of published work on co-drugs is limited but the available data suggest the co-drug concept could provide a significant therapeutic improvement in dermatological diseases. However, the applicability of the co-drug approach is subject to strict limitations pertaining mainly to the availabilithy of compatible moieties and physicochemical properties of the overall molecule.
Dr. C.M. Heard, Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3NB, UK. heard@cf.ac.uk
Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
3.8 Pharmacology (Part of: 3 Laboratory methods)