Assessing the Potential for Drug-Nanoparticle Surface Interactions to Improve Drug Penetration into the Skin

X. J. Cai, A. Woods, P. Mesquida, S. A. Jones*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
290 Downloads (Pure)


There is continued debate as to how nanomaterials enhance the passive diffusion of drugs through the skin. This study examined if drug-nanoparticle surface interactions, which occurred during topical application, had the capability to enhance percutaneous penetration. Atomic force microscopy force adhesion measurements were used to demonstrate that a model drug, tetracaine, strongly adsorbed to the surface of a negatively charged carboxyl-modified polystyrene nanoparticle (NanoPSCOOH) through both its methyl and amine functionalities (up to a 6- and 16-fold greater adhesion force respectively compared with the CH3-CH3 control). These drug-particle adhesion forces were significantly reduced (p <0.05) to values that were lower than the CH3-CH3 control measurements when tetracaine interacted with a silica nanoparticle (NanoSiO2 ). This reduction in adhesion was attributed to the lower surface charge of the NanoSiO2 (ca. -23 mV) compared to the NanoPSCOOH (ca. -40 mV), which diminished the electrostatic interactions between positive amine of tetracaine and the negative particle. Mixing NanoPSCOOH with tetracaine on the skin retarded percutaneous drug penetration compared to the control (tetracaine saturated solution without nanoparticles), but the NanoSiO2 , which still adsorbed the tetracaine, produced a 3.6-fold enhancement in percutaneous penetration compared to the same control. These data demonstrated the capability of moderate nanoparticle surface interactions that occurred within the application vehicle to promote drug percutaneous penetration.

Original languageEnglish
Pages (from-to)1375-1384
Number of pages10
JournalMolecular Pharmaceutics
Issue number4
Publication statusPublished - 4 Apr 2016


  • AFM
  • drug delivery
  • nanoparticles
  • penetration enhancement
  • skin
  • tetracaine
  • topical


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