Entrapment of silver nanoparticles in L-α-phosphatidylcholine/cholesterol-based liposomes mitigates the oxidative stress in human keratinocyte (HaCaT) cells

Eur J Pharm Biopharm. 2021 Sep:166:163-174. doi: 10.1016/j.ejpb.2021.06.006. Epub 2021 Jun 24.

Abstract

Encapsulation procedures are used to decrease the contact of toxic nanoparticles with cells; however, this field is still not well explored. Therefore, the aim of this paper was to evaluate the effect of encapsulation of silver nanoparticles in L-α-phosphatidylcholine/cholesterol-based liposomes on a human keratinocyte cell line (HaCaT). The homogenous (PdI = 0.171) spherical (~161 nm diameter) complexes were prepared by thin film hydration with the extrusion method. The UV-Vis scan and Dynamic Light Scattering measurement did not show any "free" silver nanoparticles in solutions, which was confirmed by Transmission Electron Microscope analysis. Moreover, the liposomes were tested on HaCaT cells, showing that the encapsulation process reduced the toxicity by 30%-10% at the 100 nM and 1 pM concentrations, respectively, in comparison to "free" nanoparticles, measured by resazurin reduction and lactate dehydrogenase release assays. Moreover, the caspase-3 activity was lower after 48-h treatment with LipoAgNPs than with AgNPs. The level of reactive oxygen species (ROS) after 1, 6, 48, and 72 h of treatment of HaCaT cells was significantly lower in comparison to cells treated with "bare" silver nanoparticles analyzed with the H2DCF-DA probe. The metabolic activity was strictly correlated with toxicity, indicating a lower negative impact of encapsulated nanoparticles than the "bare" ones.

Keywords: Encapsulation; Keratinocytes; Liposomes; Silver nanoparticles; Toxicity; Toxicology.

MeSH terms

  • Cholesterol / metabolism*
  • Drug Compounding / methods
  • Drug-Related Side Effects and Adverse Reactions / prevention & control
  • Dynamic Light Scattering
  • HaCaT Cells
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Liposomes
  • Metal Nanoparticles* / adverse effects
  • Metal Nanoparticles* / therapeutic use
  • Nanoparticle Drug Delivery System
  • Oxidative Stress / drug effects
  • Phosphatidylcholines / metabolism*
  • Reactive Oxygen Species / analysis
  • Silver* / pharmacology
  • Silver* / toxicity

Substances

  • Liposomes
  • Nanoparticle Drug Delivery System
  • Phosphatidylcholines
  • Reactive Oxygen Species
  • Silver
  • Cholesterol