Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles - Composition-dependent skin penetration enhancement of a dye probe and biocompatibility

Eur J Pharm Biopharm. 2017 Jul:116:66-75. doi: 10.1016/j.ejpb.2016.10.019. Epub 2016 Oct 27.

Abstract

Nanoparticles can improve topical drug delivery: size, surface properties and flexibility of polymer nanoparticles are defining its interaction with the skin. Only few studies have explored skin penetration for one series of structurally related polymer particles with systematic alteration of material composition. Here, a series of rigid poly[acrylonitrile-co-(N-vinyl pyrrolidone)] model nanoparticles stably loaded with Nile Red or Rhodamin B, respectively, was comprehensively studied for biocompatibility and functionality. Surface properties were altered by varying the molar content of hydrophilic NVP from 0 to 24.1% and particle size ranged from 35 to 244nm. Whereas irritancy and genotoxicity were not revealed, lipophilic and hydrophilic nanoparticles taken up by keratinocytes affected cell viability. Skin absorption of the particles into viable skin ex vivo was studied using Nile Red as fluorescent probe. Whilst an intact stratum corneum efficiently prevented penetration, almost complete removal of the horny layer allowed nanoparticles of smaller size and hydrophilic particles to penetrate into viable epidermis and dermis. Hence, systematic variations of nanoparticle properties allows gaining insights into critical criteria for biocompatibility and functionality of novel nanocarriers for topical drug delivery and risks associated with environmental exposure.

Keywords: Biocompatibility testing; Drug delivery systems; Nanoparticle; Poly[acrylonitrile-co-(N-vinyl pyrrolidone)]; Polymers; Skin absorption.

MeSH terms

  • Acrylonitrile / administration & dosage
  • Acrylonitrile / chemistry*
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / chemistry*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemistry, Pharmaceutical / methods
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Epidermis / metabolism*
  • Fluorescent Dyes / administration & dosage
  • Fluorescent Dyes / chemistry*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Keratinocytes / metabolism
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry*
  • Oxazines / administration & dosage
  • Oxazines / chemistry
  • Particle Size
  • Polymers / administration & dosage
  • Polymers / chemistry
  • Pyrrolidinones / administration & dosage
  • Pyrrolidinones / chemistry*
  • Skin Absorption / drug effects
  • Surface Properties

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Fluorescent Dyes
  • Oxazines
  • Polymers
  • Pyrrolidinones
  • N-vinyl-2-pyrrolidinone
  • Acrylonitrile
  • nile red