title: Localized Epidermal Drug Delivery Induced by Supramolecular Solvent Structuring.
abstract: The preferential localization of drug molecules in the epidermis of human skin is considered advantageous for a number of agents, but achieving such a delivery profile can be problematic. The aim of the present study was to assess if the manipulation of solvent supramolecular structuring in the skin could be used to promote drug residence in the epidermal tissue. Skin deposition studies showed that a 175-fold increase in the epidermal loading of a model drug diclofenac (138.65 ± 11.67 μg·cm(-2)), compared to a control (0.81 ± 0.13 μg·cm(-2)), could be achieved by colocalizing the drug with a high concentration of propylene glycol (PG) in the tissue. For such a system at 1 h postdose application, the PG flux into the skin was 9.3 mg·cm(2)·h(-1) and the PG-water ratio in the epidermis was 76:24 (v/v). At this solvent ratio infrared spectroscopy indicated that PG rich supramolecular structures, which displayed a relatively strong physical affinity for the drug, were formed. Encouraging the production of the PG-rich supermolecular structures in the epidermis by applying diclofenac to the skin using a high PG loading dose (240 μg·cm(-2)) produced an epidermal-transdermal drug distribution of 6.8:1. However, generating water-rich solvent supermolecular structures in the epidermis by applying diclofenac using a low PG loading dose (2.2 μg·cm(-2)) led to a loss of preferential epidermal localization of diclofenac in the tissue (0.7:1 epidermal-transdermal drug distribution). This change in diclofenac skin deposition profile in response to PG variations and the accompanying FTIR data supported the notion that supramolecular solvent structures could control drug accumulation in the human epidermis.
authors.affiliation: Institute of Pharmaceutical Science, School of Life Sciences & Medicine, King's College London , Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, U.K.
authors.forename: F
authors.initials: F
authors.lastname: Benaouda
authors.affiliation: Institute of Pharmaceutical Science, School of Life Sciences & Medicine, King's College London , Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, U.K.
authors.forename: S A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Institute of Pharmaceutical Science, School of Life Sciences & Medicine, King's College London , Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, U.K.
authors.forename: G P
authors.initials: GP
authors.lastname: Martin
authors.affiliation: MedPharm Ltd. , Unit 3/Chancellor Court, 50 Occam Road, Surrey Research Park, Guildford, GU2 7AB, U.K.|School of Pharmacy, University of Herts , College Lane Campus, Hatfield, Herts AL10 9AB, U.K.
authors.forename: M B
authors.initials: MB
authors.lastname: Brown
mesh_terms: D000279:Administration, Cutaneous; D016503:Drug Delivery Systems / Q000379:methods; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008962:Models, Theoretical; D019946:Propylene Glycol / Q000737:chemistry; D012869:Skin Absorption; D012997:Solvents / Q000737:chemistry*
chemical_list: D012997:Solvents; D019946:Propylene Glycol
keywords: Human skin; diclofenac; propylene glycol; supramolecular structuring; topical delivery