Enhanced colloidal stability and protein resistance of layered double hydroxide nanoparticles with phosphonic acid-terminated PEG coating for drug delivery

J Colloid Interface Sci. 2018 Jul 1:521:242-251. doi: 10.1016/j.jcis.2018.03.006. Epub 2018 Mar 3.

Abstract

Conjugating nanoparticles with polyethylene glycol (PEG) is a useful strategy to improve the colloidal and biological stability of nanoparticles. However, studies on PEGylation of two-dimensional layered double hydroxide (LDH) nanoparticles are very limited. The present work reported two functionalization approaches to synthesize PEG-conjugated LDH nanoparticles by introducing phosphonic acid terminated PEG before and after LDH aging. The successful PEGylation was confirmed and suggested to be via electrostatic interaction and a ligand exchange process. Different functionalization approaches resulted in different binding types of PEG on/in LDH nanoparticles. The PEG coating maintained the dispersity of LDH nanoparticles in water and saline with the feeding mass ratio of 1:1. Further colloidal stability tests of PEGylated LDHs revealed that the PEGylated LDH dispersity was affected by the feeding mass ratio of PEG/LDH, the molar weight of PEG and anions intercalated in the LDHs. In a test to determine the extent of non-specific protein adsorption, the PEGylation was effective at resisting non-specific bovine serum albumin adsorption on LDH nanoparticles with both functionalization methods investigated. Moreover, PEGylated LDH nanoparticles had no effect on cell viability up to 500 µg/mL, and demonstrated enhanced cellular uptake in a SK-MEL-28 cell culture. The results in this work indicate that conjugating phosphonic acid-terminated PEG on LDH nanoparticles is a promising strategy to improve the colloidal and biological stability of LDHs for biomedical applications.

Keywords: Layered double hydroxide; Nanoparticle; Non-specific protein adsorption; PEGylation; Stability.

MeSH terms

  • Adsorption
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colloids
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Excipients / chemistry
  • Fluorescein-5-isothiocyanate / chemistry
  • Fluorescent Dyes / chemistry
  • Humans
  • Hydroxides / chemistry*
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Particle Size
  • Phosphorous Acids / chemistry*
  • Polyethylene Glycols / chemistry*
  • Serum Albumin, Bovine / chemistry
  • Solubility
  • Surface Properties
  • Water

Substances

  • Colloids
  • Drug Carriers
  • Excipients
  • Fluorescent Dyes
  • Hydroxides
  • Phosphorous Acids
  • Water
  • Serum Albumin, Bovine
  • Polyethylene Glycols
  • Fluorescein-5-isothiocyanate