Metabolomic profiles altered by erlotinib encapsulated in poly(lactide-co-glycolide) nanoparticles in non-small cell lung cancer.

Abstract

Objective: This research is focused on the metabolomics and cytotoxic effects of the anticancer drug erlotinib encapsulated in poly(lactide-co-glycolide) nanoparticles on non-small cell lung cancer (NSCLC) cell lines.

Methods: Uniform-sized nanoparticles (0.325 and 0.068 PDI) with mean diameters of 264.5 and 268.4 nm for blank and erlotinib-PLGA nanoparticles (nanodrugs-NDs) were formulated, respectively. The encapsulation efficiency of prepared nanoparticles was found to be 90.1%. 36% of erlotinib was released from PLGA nanoparticles within 24 h, and the maximum sustained release was 43% at 72 h. The metabolomic and cytotoxic effects of ND were evaluated.

Results: The Bax/Bcl-2 ratio was the lowest in the nanodrug group at 72 h, showing increased apoptosis, indicating that the most effective drug formulation is the combined nanoparticle at 72 h. The metabolomic studies revealed changing amino acids, antioxidant molecules, and carbohydrate profiles. The most significant changes were obtained in pathways related to the synthesis of p-glycoprotein, which is the principal protein for drug efflux and causes drug resistance. The lowest levels of amino acids and polyamines like serine, threonine, spermine, and spermidine were obtained at 72 h with erlotinib encapsulated in poly(lactide-co-glycolide) (PLGA) nanoparticles, showing that the drug resistance may in part be overcome with this nanoparticles.

Conclusion: The encapsulation of erlotinib with PLGA showed effects and influenced critical metabolic pathways, especially pointing out the need to lower drug resistance and signifying it's potential use as an effective treatment strategy for NSCLC.