CD44 targeting hyaluronic acid coated lapatinib nanocrystals foster the efficacy against triple-negative breast cancer

Nanomedicine. 2018 Feb;14(2):327-337. doi: 10.1016/j.nano.2017.10.010. Epub 2017 Nov 9.

Abstract

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than the counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs treatment caused significant retardation of tumor growth and overall increase in animal survival probability because of their higher tumor localization, increased residence time. Our findings clearly suggest that HA coated LPT-NCs formulation enhances the activity of LPT against triple negative breast cancer. It exhibited magnificent therapeutic outcome at low dose thus presenting a strategy to reduce dose administrations and minimize dose related toxicity.

Keywords: Hyaluronic acid; Lapatinib; Nanocrystals; Triple-negative breast cancer; Tykerb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Female
  • Hyaluronan Receptors / antagonists & inhibitors*
  • Hyaluronic Acid / chemistry*
  • Lapatinib / chemistry
  • Lapatinib / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • CD44 protein, human
  • Hyaluronan Receptors
  • Lapatinib
  • Hyaluronic Acid