Cabazitaxel-loaded redox-responsive nanocarrier based on d-alpha-tocopheryl-chitosan and hyaluronic acid for improved anti-tumor efficacy in DMBA-induced breast cancer model

Abstract

The study involved the formulation of cabazitaxel loaded D-alpha-tocopheryl succinate/chitosan conjugate (CSVE) and hyaluronic acid (HA) based redox-responsive nanoparticles crosslinked using 3,3′-dithiodipropionic acid (DTPA). The nanoparticle surface was functionalized with cetuximab (Cmab) to give CSVE/HA/DTPA/Cmab NP for EGFR targeted delivery of the payload. The formulations were subjected to particle analysis, morphological assessment, solid-state characterization, and in vitro drug release studies. The results showed cationic, sub-200 nm sized spherical particles with the glutathione-responsive release of cabazitaxel. In vitro studies revealed a marked decrease in the IC₅₀ value, improved cellular uptake, and a superior apoptotic effect. To determine the in vivo efficacy of the formulation, pharmacokinetic assessment, tumor regression analysis, and survival analysis were performed. The nanoparticles showed improved pharmacokinetic and anti-tumor efficacy compared to free cabazitaxel. The prepared nanoparticles demonstrated immense potential in targeted delivery of the payload for enhanced breast cancer therapy.