Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery

ACS Appl Mater Interfaces. 2018 Jun 13;10(23):19336-19346. doi: 10.1021/acsami.8b01154. Epub 2018 May 30.

Abstract

In this study, novel hydrogel nanoparticles with dual triggerable release properties based on fibrous structural proteins (keratin) and thermoresponsive copolymers (Pluronic) are introduced. Nanoparticles were used for curcumin delivery as effective and safe anticancer agents, the hydrophobicity of which has limited their clinical applications. A drug was loaded into hydrogel nanoparticles by a single-step nanoprecipitation method. The drug-loaded nanoparticles had an average diameter of 165 and 66 nm at 25 and 37 °C, respectively. It was shown that the drug loading efficiency could be enhanced through crosslinking of the disulfide bonds in keratin. Crosslinking provided a targeted release profile under reductive conditions using an in vivo agent, glutathione (GSH), or in the presence of trypsin. Cytocompatibility assay using HeLa and L929 fibroblast cells exhibited no adverse effect of nanoparticles on cell viability up to 1 mg/mL. Besides, the green fluorescence of curcumin confirmed the uptake of drug-loaded nanoparticles by cancer cells. The redox and temperature-sensitive nanoparticles are potentially useable for the efficient delivery of hydrophobic drugs to targeted regions having a triggerable release profile.

Keywords: Pluronic conjugates; drug delivery; hydrogel nanoparticles; keratin biopolymer; stimuli-responsive copolymer.

MeSH terms

  • Antineoplastic Agents
  • Cell Line, Tumor
  • Cell Survival
  • Drug Carriers
  • Drug Delivery Systems
  • Humans
  • Hydrogels
  • Nanoparticles*
  • Polymers

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Hydrogels
  • Polymers