Study on co-delivery of pemetrexed disodium and Bcl-2 siRNA by poly- γ-glutamic acid-modified cationic liposomes for the inhibition of NSCLC

Drug Dev Ind Pharm. 2023 Feb 20:1-18. doi: 10.1080/03639045.2023.2182125. Online ahead of print.ABSTRACTDue to the complexity of pathophysiology of non-small cell lung cancer (NSCLC) and susceptibility of single chemotherapy to drug resistance, the combination of drugs and small interfering RNA (siRNA) may produce desired therapeutic effect on NSCLC through action of multiple pathways. We designed to develop poly-γ-glutamic acid-modified cationic liposomes (γ-PGA-CL) to co-deliver pemetrexed disodium (PMX) and siRNA to treat NSCLC. Firstly, γ-PGA was modified on surface of PMX and siRNA co-loaded cationic liposomes by electrostatic interaction (γ-PGA modified PMX/siRNA-CL). In order to evaluate whether the prepared γ-PGA modified PMX/siRNA-CL could be taken up by tumor cells and exert significant anti-tumor effects, in vitro and in vivo studies were performed, with A549 cells and LLC-bearing BABL/c mice as experimental models, respectively. The particle size and zeta potential of γ-PGA modified PMX/siRNA-CL was (222.07 ± 1.23) nm and (-11.38 ± 1.44) mV. Preliminary stability experiment showed the complex could protect siRNA from degradation. In vitro cell uptake experiment indicated the complex group exerted stronger fluorescence intensity and expressed higher flow detection value. Cytotoxicity study showed the cell survival rate of γ-PGA-CL was (74.68 ± 0.94)%. Polymerase chain reaction (PCR) analysis and western blot technology displayed that the complex could inh...
Source: Drug Development and Industrial Pharmacy - Category: Drugs & Pharmacology Authors: Source Type: research