Core-multishell nanocarriers: Transport and release of dexamethasone probed by soft X-ray spectromicroscopy

J Control Release. 2016 Nov 28:242:64-70. doi: 10.1016/j.jconrel.2016.08.028. Epub 2016 Aug 24.

Abstract

Label-free detection of core-multishell (CMS) nanocarriers and the anti-inflammatory drug dexamethasone is reported. Selective excitation by tunable soft X-rays in the O 1s-regime is used for probing either the CMS nanocarrier or the drug. Furthermore, the drug loading efficiency into CMS nanocarriers is determined by X-ray spectroscopy. The drug-loaded nanocarriers were topically applied to human skin explants providing insights into the penetration and drug release processes. It is shown that the core-multishell nanocarriers remain in the stratum corneum when applied for 100min to 1000min. Dexamethasone, if applied topically to human ex vivo skin explants using different formulations, shows a vehicle-dependent penetration behavior. Highest local drug concentrations are found in the stratum corneum as well as in the viable epidermis. If the drug is loaded to core-multishell nanocarriers, the concentration of the free drug is low in the stratum corneum and is enhanced in the viable epidermis as compared to other drug formulations. The present results provide insights into the penetration of drug nanocarriers as well as the mechanisms of controlled drug release from CMS nanocarriers in human skin. They are also compared to related work using dye-labeled nanocarriers and dyes that were used as model drugs.

Keywords: Core-multishell nanocarriers; Drug delivery; Human skin; X-ray microscopy.

MeSH terms

  • Administration, Cutaneous
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Biological Transport
  • Chemistry, Pharmaceutical / methods
  • Delayed-Action Preparations
  • Dexamethasone / administration & dosage*
  • Dexamethasone / pharmacokinetics
  • Drug Carriers / chemistry*
  • Drug Delivery Systems*
  • Drug Liberation
  • Humans
  • Microscopy, Atomic Force / methods
  • Nanoparticles*
  • Skin / metabolism
  • Skin Absorption
  • Time Factors
  • X-Ray Absorption Spectroscopy / methods

Substances

  • Anti-Inflammatory Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Dexamethasone