Electrosprayed nanocomposites based on hyaluronic acid derivative and Soluplus for tumor-targeted drug delivery

Colloids Surf B Biointerfaces. 2016 Sep 1:145:267-274. doi: 10.1016/j.colsurfb.2016.05.009. Epub 2016 May 6.

Abstract

Nanocomposite (NC) based on hyaluronic acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.

Keywords: CD44 receptor; Electrospraying; Nanocomposite; Resveratrol; Tumor targeting.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Ceramides / chemistry
  • Drug Delivery Systems*
  • Drug Liberation
  • Endocytosis / drug effects
  • Fluorescence
  • Hyaluronic Acid / chemistry*
  • Male
  • Mice
  • Nanocomposites / chemistry*
  • Nanocomposites / ultrastructure
  • Polyethylene Glycols / chemistry*
  • Polyvinyls / chemistry*
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacokinetics
  • Stilbenes / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Ceramides
  • Polyvinyls
  • Stilbenes
  • polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
  • Polyethylene Glycols
  • Hyaluronic Acid
  • Resveratrol