CD44 targeting biocompatible and biodegradable hyaluronic acid cross-linked zein nanogels for curcumin delivery to cancer cells: In vitro and in vivo evaluation

J Control Release. 2018 Jun 28:280:20-30. doi: 10.1016/j.jconrel.2018.04.050. Epub 2018 May 1.

Abstract

In this study, we developed novel hyaluronic acid cross-linked zein nanogels (HA-Zein NGs) to deliver the potential anticancer agent curcumin (CRC), a naturally occurring phytochemical drug in cancer cells. In vitro studies showed that they are highly compatible with the tested cell lines. They showed CD44 specific uptake in CT26 cell line more than by the CD44 receptor pre-inhibited CT26 cells. The CRC encapsulated HA-Zein NGs (HA-Zein-CRC NGs) found to exert a specific toxicity against CT26 sparing healthy normal fibroblast cells in vitro. The apoptotic effects were further confirmed with flow cytometry showing that the HA-Zein-CRC NGs exhibited high anticancer activity against the CT26 cells. The in vivo bio-distribution with a CT26 tumor model showed their high tumor accumulation thereby improved antitumor efficacy with a low dosage of CRC, compared to the previous reports. Thus, the preclinical studies clearly showed that these novel HA-Zein NGs would be highly beneficial in encapsulating hydrophobic drugs with improved pharmacokinetics thereby enhancing the therapeutic outcomes.

Keywords: Curcumin; Enhanced bio distribution and Anti-cancer efficacy; HA-Zein NGs; In vitro stability; Selective toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cross-Linking Reagents / chemistry
  • Curcumin / chemistry*
  • Curcumin / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Drug Stability
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Hyaluronic Acid / chemistry*
  • Hydrophobic and Hydrophilic Interactions
  • Mice, Inbred BALB C
  • Molecular Targeted Therapy / methods
  • Nanoparticles / chemistry*
  • Polymerization
  • Tissue Distribution
  • Zein / chemistry*

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • CD44 protein, human
  • Cross-Linking Reagents
  • Drug Carriers
  • Hyaluronan Receptors
  • Hyaluronic Acid
  • Zein
  • Curcumin