Microneedle/nanoencapsulation-mediated transdermal delivery: mechanistic insights

Yasmine A. Gomaa, Martin J. Garland, Fiona J. McInnes, Ryan F. Donnelly, Labiba K. El-Khordagui*, Clive G. Wilson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)
207 Downloads (Pure)

Abstract

A systematic study was undertaken to gain more insight into the mechanism of transdermal delivery of nanoencapsulated model dyes across microneedle (MN)-treated skin, a complex process not yet explored. Rhodamine B (Rh B) and fluorescein isothiocyanate (FITC) as model hydrophilic and hydrophobic small/medium-size molecules, respectively, were encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and delivered through full thickness porcine skin pretreated with MN array. Permeation through MN-treated skin was affected by physicochemical characteristics of NPs and the encapsulated dyes. Dye flux was enhanced by smaller particle size, hydrophilicity, and negative zeta potential of NPs. Regarding encapsulated dyes, solubility at physiological pH and potential interaction with skin proteins proved to outweigh molecular weight as determinants of skin permeation. Data were verified using confocal laser scanning microscopy imaging. Findings coupled with the literature data are supportive of a mechanism involving influx of NPs, particularly of smaller size, deep into MN-created channels, generating depot dye-rich reservoirs. Molecular diffusion of the released dye across viable skin layers proceeds at a rate determined by its molecular characteristics. Data obtained provide mechanistic information of importance to the development of formulation strategies for more effective intradermal and transdermal MN-mediated delivery of nanoencapsulated therapeutic agents.

Original languageEnglish
Pages (from-to)145-155
Number of pages11
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume86
Issue number2
Early online date24 Feb 2013
DOIs
Publication statusPublished - Feb 2014

Keywords

  • confocal laser scanning microscopy
  • fluorescein isothicoyanate
  • microneedles
  • PLGA nanoparticles
  • Rhodamine B
  • skin permeation
  • transdermal delivery

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