Time-resolved fluorescence microscopy with phasor analysis for visualizing multicomponent topical drug distribution within human skin

Sci Rep. 2020 Mar 24;10(1):5360. doi: 10.1038/s41598-020-62406-z.

Abstract

Understanding a drug candidate's pharmacokinetic (PK) parameters is a challenging but essential aspect of drug development. Investigating the penetration and distribution of a topical drug's active pharmaceutical ingredient (API) allows for evaluating drug delivery and efficacy, which is necessary to ensure drug viability. A topical gel (BPX-05) was recently developed to treat moderate to severe acne vulgaris by directly delivering the combination of the topical antibiotic minocycline and the retinoid tazarotene to the pilosebaceous unit of the dermis. In order to evaluate the uptake of APIs within human facial skin and confirm accurate drug delivery, a selective visualization method to monitor and quantify local drug distributions within the skin was developed. This approach uses fluorescence lifetime imaging microscopy (FLIM) paired with a multicomponent phasor analysis algorithm to visualize drug localization. As minocycline and tazarotene have distinct fluorescence lifetimes from the lifetime of the skin's autofluorescence, these two APIs are viable targets for distinct visualization via FLIM. Here, we demonstrate that the analysis of the resulting FLIM output can be used to determine local distributions of minocycline and tazarotene within the skin. This approach is generalizable and can be applied to many multicomponent fluorescence lifetime imaging targets that require cellular resolution and molecular specificity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Algorithms
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / pharmacokinetics
  • Drug Combinations
  • Face
  • Fluorescence
  • Gels / administration & dosage
  • Humans
  • Image Processing, Computer-Assisted
  • Microscopy, Fluorescence / methods*
  • Minocycline / administration & dosage
  • Minocycline / pharmacokinetics*
  • Molecular Imaging / methods
  • Nicotinic Acids / administration & dosage
  • Nicotinic Acids / pharmacokinetics*
  • Skin / chemistry
  • Skin / diagnostic imaging
  • Skin / drug effects*
  • Spectrometry, Fluorescence

Substances

  • Dermatologic Agents
  • Drug Combinations
  • Gels
  • Nicotinic Acids
  • tazarotene
  • Minocycline