Crizotinib-loaded polymeric nanoparticles in lung cancer chemotherapy

The study describes the development of polylactide-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS)-based nanosystem as a carrier of crizotinib (CZT) to achieve superior anticancer efficacy in lung cancer therapy. We have demonstrated that block copolymer and hydrophobic drug is capable of self-assembling into a very stable nanocarrier, with suitable properties that allow their application for cancer drug delivery. Drug release study showed a sustained release pattern as a result of entrapment in the hydrophobic core of micelles. CZT/PT NP showed a noticeable cytotoxic effect in NCIH3122 lung cancer cells in a dose-dependent manner. Furthermore, morphological imaging and Live/Dead assay revealed a superior anticancer efficacy for nanoformulations. The polymeric nanoparticle showed a predominant presence in the cytoplasmic region of cell, indicating a typical endocytosis-mediated cellular uptake. The annexin V/PI staining-based apoptosis assay showed a remarkable ~40 % apoptosis (early and late apoptosis cells) comparing to only ~25 % apoptosis by free CZT. Taken together, Vitamin E TPGS-modified PLA nanoparticles would be a potential drug delivery system to increase the chemotherapeutic efficacy of CZT in lung cancer chemotherapy.