Co-delivery of metformin and Silibinin with biocompatible PLGA–PEG copolymer nanoparticles for the treatment of non-small lung cancer

Background: Lung cancer is a disease characterized by the uncontrolled growth of the cell in the lung tissue. Considering the significant statistics of lung cancer that accounts for about 26% of deaths compared to total cancers, and current treatments include surgery, chemotherapy, radiation therapy, etc., these commonly mentioned methods Do not provide acceptable returns. Therefore, the use of an effective method with the least side effects and the greatest possible impact is necessary. Nanoparticle (NP)-based combinational chemotherapy has been proposed as a potent approach for improving intracellular drug concentrations and attaining synergistic effects in lung cancer therapy. Here, two wellknown herbal substances, Metformin (MET) and Silibinin (sil), were coencapsulated in PEGylated PLGA NPs and investigated their synergistic inhibitory effect against A549 cancer cellsMaterials and Methods: Silybin and metformin were loaded onto synthesized nanoparticles. Characterization of nanoformulated drugs was determined using DLS, FTIR, TEM, and SEM. Drug release study was performed using dialysis method. MTT and real-time PCR assays were applied to evaluate the cytotoxic effects of free and nanoencapsulated drugs on expression level of hTERT in A549 cellsResults: The results showed that free drugs and formulations exhibited a dose-dependent cytotoxicity against A549 cells and especially, met–Sil–PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of cancer cells than the other groups (p<.05). Real-time PCR results showed that sil, Met and combination of Met–sil in free and encapsulated forms inhibited hTERT gene expression. It was found that Met–sil–PLGA/PEG NPs in relative to free combination could further decline hTERT expression in all concentration (p<.05).Conclusion: In conclusion, it is supposed that nano-encapsulation of Met–sil into polymeric PLGA-PEG NPs may be a convenient drug delivery system to enhance its anticancer effects for lung cancer therapy.