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Confocal Raman Spectroscopic Characterization of Dermatopharmacokinetics Ex Vivo.
Zarmpi, Panagiota; Tabosa, M Alice Maciel; Vitry, Pauline; Bunge, Annette L; Belsey, Natalie A; Tsikritsis, Dimitrios; Woodman, Timothy J; Delgado-Charro, M Begoña; Guy, Richard H.
Afiliación
  • Zarmpi P; Department of Life Sciences, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
  • Tabosa MAM; Department of Life Sciences, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
  • Vitry P; Department of Life Sciences, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
  • Bunge AL; Department of Chemical & Biological Engineering, Colorado School of Mines, Golden, Colorado 80401, United States.
  • Belsey NA; National Physical Laboratory, Teddington TW11 0LW, U.K.
  • Tsikritsis D; School of Chemistry & Chemical Engineering, University of Surrey, Guildford GU2 7XH, U.K.
  • Woodman TJ; National Physical Laboratory, Teddington TW11 0LW, U.K.
  • Delgado-Charro MB; Department of Life Sciences, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
  • Guy RH; Department of Life Sciences, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
Mol Pharm ; 20(11): 5910-5920, 2023 11 06.
Article en En | MEDLINE | ID: mdl-37801410
Confocal Raman spectroscopy is being assessed as a tool with which to quantify the rate and extent of drug uptake to and its clearance from target sites of action within the viable epidermis below the skin's stratum corneum (SC) barrier. The objective of this research was to confirm that Raman can interrogate drug disposition within the living layers of the skin (where many topical drugs elicit their pharmacological effects) and to identify procedures by which Raman signal attenuation with increasing skin depth may be corrected and normalized so that metrics descriptive of topical bioavailability may be identified. It was first shown in experiments on skin cross-sections parallel to the skin surface that the amide I signal, originating primarily from keratin, was quite constant with depth into the skin and could be used to correct for signal attenuation when confocal Raman data were acquired in a "top-down" fashion. Then, using 4-cyanophenol (CP) as a model skin penetrant with a strong Raman-active C≡N functionality, a series of uptake and clearance experiments, performed as a function of time, demonstrated clearly that normalized spectroscopic data were able to detect the penetrant to at least 40-80 µm into the skin and to distinguish the disposition of CP from different vehicles. Metrics related to local bioavailability (and potentially bioequivalence) included areas under the normalized C≡N signal versus depth profiles and elimination rate constants deduced post-removal of the formulations. Finally, Raman measurements were made with an approved dermatological drug, crisaborole, for which delivery from a fully saturated formulation into the skin layers just below the SC was detectable.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Absorción Cutánea / Espectrometría Raman Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Absorción Cutánea / Espectrometría Raman Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos