title: Effects of permeation enhancers on flufenamic acid delivery in Ex vivo human skin by confocal Raman microscopy.
abstract: For effective topical delivery, a drug must cross the stratum corneum (SC) barrier into viable tissue. The use of permeation enhancers is a widespread approach for barrier modification. In the current study, flufenamic acid (FluA), a non-steroidal anti-inflammatory drug, is a model agent for investigating the influence of hydrophobic versus hydrophilic enhancers. In separate experiments, FluA in octanol or propylene glycol/ethanol (75/25) is applied to the SC for varying times followed by confocal Raman microscopic mapping of drug and enhancer penetration and spatial distribution. Deuterated versions of the enhancers permit us to spectroscopically distinguish the exogenous chemicals from the endogenous SC lipids without affecting penetration parameters. The FluA pathway is tracked by the CC stretching mode at ∼1618cm(-1). Discrete, small inclusions of both enhancers are observed throughout the SC. High concentrations of FluA are co-localized with octanol domains which appear to provide a pathway to the viable epidermis for the drug. In contrast, FluA concentrates in the upper SC when using the hydrophilic agent and endogenous lipids appear unperturbed in regions outside the enhancer pockets. The ability to examine perturbations to endogenous ultrastructure and molecular structure in skin while tracking penetration pathways provides insight into delivery mechanisms.
authors.affiliation: Rutgers University, Department of Chemistry, 73 Warren Street, Newark, NJ 07102, United States.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Pyatski
authors.affiliation: Rutgers University, Department of Chemistry, 73 Warren Street, Newark, NJ 07102, United States.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Rutgers University, Department of Chemistry, 73 Warren Street, Newark, NJ 07102, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Mendelsohn
authors.affiliation: Rutgers University, Department of Chemistry, 73 Warren Street, Newark, NJ 07102, United States. Electronic address: flach@andromeda.rutgers.edu.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Flach
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000279:Administration, Cutaneous; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D000431:Ethanol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005439:Flufenamic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry; D018613:Microscopy, Confocal; D019946:Propylene Glycol / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013059:Spectrum Analysis, Raman
chemical_list: D000893:Anti-Inflammatory Agents; D005079:Excipients; D008055:Lipids; D000431:Ethanol; D005439:Flufenamic Acid; D019946:Propylene Glycol; D020003:1-Octanol
keywords: Chemical permeation enhancer; Confocal Raman microscopy; Cutaneous penetration; Flufenamic acid; Skin