Satish Agrawal
CSIR-Central Drug Research Institute, India
Title: CD44 targeting hyaluronic acid coated lapatinib nanocrystals for fostered efficacy against triple-negative breast cancer
Biography
Biography: Satish Agrawal
Abstract
Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. However, there are many drawbacks associated with LPT that limits its therapeutic activity. In order to address the limitations associated with LPT, we have prepared its nanocrystals (LPT-NCs) those were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed investigation of LPT-HA-NCs showed the superior anticancer activity than its counterparts LPT-NCs and free LPT. LPT-HA-NCs were associated with increased cytotoxicity and the enhanced uptake in MDA-MB-231 cells due to active targeting to CD44 and EGFR receptors. It was also evident that the LPT-HA-NCs induced apoptosis is due to the Fas and mitochondrial membrane potential dependent pathway. The results of in-vitro studies were followed very well in the in-vivo studies. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs not only increased the residence time of LPT, but also targeted the tumor, reduced the tumor burden, and increased overall survival. 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.