Dual drug delivery of Paclitaxel and Curcumin via hyaluronic acid functionalized nanoparticles for improved breast cancer therapy.

Abstract

Breast cancer has high mortality rate among women. Though paclitaxel is one of the important drugs used, but frequent use will lead to drug resistance. Nuclear factor kappa B (NFƘB) a transcription factor will be up regulated with frequent use of paclitaxel, and this increases drug resistance in cancer cells. Usage of curcumin will down regulate the NFƘB and using both the drugs in combination with different mechanisms of action has shown synergistic effects and reduces NFƘB expression in cancer cells. To reduce the systemic toxicity, low intracellular uptake and low bioavailability, nano-based therapeutics were used. To improve the targeting ability of the drug to the cancer cells, Hyaluronic acid (HA) is used as a targeting moiety on the surface of the nanoparticles (NP). The study focuses on formulating a Hyaluronic acid (HA) surface functionalized Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) encapsulated with Paclitaxel (PTX) or Curcumin (CUR) to target CD44v expressed on breast cancer cells. HA surface functionalized NPs encapsulated with only PTX or in combination with CUR were treated against MCF-7 breast cancer cells. We found that HA surface functionalized NPs with combination of PTX and CUR has substantially increased cytotoxicity compared to non-surface functionalized NPs and free drugs and 2.5-fold increased cellular uptake of NPs compared to free drugs. We also found that NFKB activity reduces significantly with the use of CUR with PTX. From the results, we can conclude that combination of drugs in HA surface functionalized NPs will be useful for breast cancer therapy.