Advance nanotherapeutic approach for systemic co-delivery of mitoxantrone loaded chitosan coated PLGA nanoparticles to improve the chemotherapy against human non-small cell lung cancer

Abstract

Poly(lactide-co-glycolide) nanoparticles (PLGA NPs) are a type of polymeric nanoparticles that offer benefits over metallic NPs, such as the capacity to sustain therapeutic drug levels for extended periods. In the current study, in order to enhance the solubility, stability, and anti-cancer effect of the mitoxantrone drug (Mtx), mitoxantrone-loaded chitosan-coated PLGA NPs (Mtx-loaded Cht-PLGA NPs) were synthesized. Mtx-loaded Cht-PLGA NPs were coated with Cht to improve mucoadhesiveness and colloidal stability. The synthesized NPs were checked for their size, morphology, zeta potential, encapsulation efficiency, FTIR and in vitro release studies. The anti-cancer potential of Mtx-loaded Cht-PLGA NPs were assessed in the A-549 lung cancer cell lines. Additionally, compared to pure Mtx, the viability of A-549 cells markedly decline with increasing concentrations of Mtx-loaded Cht-PLGA NPs. The cellular uptake study also confirms that chitosan coating greatly enhanced the uptake of the nanoparticles. Further, the ability to stimulate the reactive oxygen species (ROS) generation at the IC50 concentration of Mtx-loaded Cht-PLGA NPs was confirmed by using carboxy-2,7-dichloro-dihydro-fluorescein diacetate. Further, the western blotting revealed the down-regulation of TGF-β, vimentin, and upregulation of p53. This study reveals that the developed mitoxantrone-loaded cationically charged polymeric nano vehicle would be effectively less cytotoxic and have improved efficacy against lung cancer.