Biocompatible, controlled-release remdesivir-loaded liposomes tackling the telomerase activity of Non-Small cell lung cancer cells: Preparation, characterization, in vitro biological evaluation, and molecular docking analysis

Non-small cell lung cancer (NSCLC) is a global leading cause of cancer mortality. Herein, remdesivir (RDV) was loaded into biocompatible liposomes (RDV-Lips) composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol, and polyethylene glycol hexadecyl ether (Brij-58) to enhance its solubility and anticancer efficiency. The study highlighted the possible RDV-induced underlying events, emphasizing its inhibitory potential of telomerase activity through in-silico docking and in vitro studies. RDV-Lips were developed using thinfilm hydration and then subjected to physicochemical characterizations. The selected formulations were evaluated for their stability, in vitro release, and in vitro anticancer activity. The size range of RDV-Lips was 83.8-157.9 nm with a polydispersity index (PDI) lower than 0.23 and entrapment exceeded 93%. The cholesterol content of RDV-Lips offered a control point of RDV release, where high and low concentrations exerted slow and fast release patterns, respectively. RDV-Lips showed enhanced anticancer activity and selectivity. They inhibited colony formation, increased lipid peroxidation, induced apoptosis, and inhibited the telomerase activity in a dose-dependent manner. In conclusion, RDV-Lips overcame RDV solubility problems and enhanced its anticancer efficiency. RDV could be a potential therapy against NSCLC via induction of oxidative stress and inhibition of the telomerase activity, which, in turn, restricts unlimited cellular proliferation and apoptosis induction.