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In situ biodistribution and residency of a topical anti-inflammatory using fluorescence lifetime imaging microscopy.
Alex, A; Frey, S; Angelene, H; Neitzel, C D; Li, J; Bower, A J; Spillman, D R; Marjanovic, M; Chaney, E J; Medler, J L; Lee, W; Vasist Johnson, L S; Boppart, S A; Arp, Z.
Afiliação
  • Alex A; GSK, Collegeville, PA, U.S.A.
  • Frey S; GSK, Collegeville, PA, U.S.A.
  • Angelene H; GSK, Bangalore, India.
  • Neitzel CD; Carle Foundation Hospital, Urbana, IL, U.S.A.
  • Li J; University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.
  • Bower AJ; University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.
  • Spillman DR; University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.
  • Marjanovic M; University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.
  • Chaney EJ; University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.
  • Medler JL; Carle Foundation Hospital, Urbana, IL, U.S.A.
  • Lee W; Carle Foundation Hospital, Urbana, IL, U.S.A.
  • Vasist Johnson LS; GSK, Collegeville, PA, U.S.A.
  • Boppart SA; University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.
  • Arp Z; GSK, Collegeville, PA, U.S.A.
Br J Dermatol ; 179(6): 1342-1350, 2018 12.
Article em En | MEDLINE | ID: mdl-29989149
BACKGROUND: GSK2894512 is a topically delivered investigational drug being developed for treatment of atopic dermatitis and psoriasis. OBJECTIVES: To investigate, in a phase I clinical trial, the spatial biodistribution and residency of GSK2894512 within the epidermis and dermis of healthy human participants noninvasively using fluorescence lifetime imaging microscopy (FLIM). METHODS: Two topical drug formulations containing GSK2894512 1% were applied to the right and left forearms of six participants for seven consecutive days, followed by seven days of observation for residency. FLIM images were obtained daily throughout the study, approximately every 24 h. During the treatment phase of the study, images were collected from each participant pretreatment, reflecting the residual dose from the previous day. Three punch biopsies from each participant of one formulation was obtained from the treated region during the post-treatment follow-up period between days 8 and 14 for comparison with FLIM results. RESULTS: Cellular and subcellular features associated with different epidermal and dermal layers were visualized noninvasively, down to a depth of 200 µm. Results yielded three-dimensional maps of GSK2894512 spatial distribution and residency over time. This fluorescence data provided a marker that was used as a monitor for day-to-day variance of drug presence and residency postapplication. CONCLUSIONS: The results suggest FLIM could be a viable alternative to skin biopsies without the usual patient discomfort and limitations, thereby enabling the direct measurement of skin distribution through longitudinal monitoring. These results are the first step in establishing the unique capabilities that multiphoton imaging could provide to patients through noninvasive drug detection.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resorcinóis / Estilbenos / Anti-Inflamatórios não Esteroides / Microscopia de Fluorescência por Excitação Multifotônica / Fármacos Dermatológicos / Microscopia Intravital Limite: Adult / Humans / Male Idioma: En Revista: Br J Dermatol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resorcinóis / Estilbenos / Anti-Inflamatórios não Esteroides / Microscopia de Fluorescência por Excitação Multifotônica / Fármacos Dermatológicos / Microscopia Intravital Limite: Adult / Humans / Male Idioma: En Revista: Br J Dermatol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido