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Cationic solid lipid nanoparticles for co-delivery of paclitaxel and siRNA
Yong Hee Yu, Eunjoong Kim, Dai Eui Park, Gayong Shim, Sangbin Lee, Young Bong Kim, Chan-Wha Kim, Yu-Kyoung Oh
European Journal of Pharmaceutics and Biopharmaceutics (SCIE)
In this study, we formulated cationic solid lipid nanoparticles (cSLN) for co-delivery of paclitaxel (PTX) and siRNA. 1,2-Dioleoyl-sn-glycero-3-ethylphosphocholine-based cSLN were prepared by emulsification solidification methods. PTX-loaded cSLN (PcSLN) were characterized by zeta potential and gel retardation of complexes with small interfering RNA (siRNA). The sizes of PcSLN did not significantly differ from those of empty cSLN without PTX (EcSLN). The use of cSLN increased the cellular uptake of fluorescent dsRNA in human epithelial carcinoma KB cells, with PcSLN complexed to fluorescence-labeled dsRNA promoting the greatest uptake. For co-delivery of therapeutic siRNA, human MCL1-specific siRNA (siMCL1) was complexed with PcSLN; luciferase-specific siRNA (siGL2) complexed to EcSLN or PcSLN was used as a control. MCL1 mRNA levels were significantly reduced in KB cells treated with siMCL1 complexed to PcSLN, but not in groups treated with siMCL alone or siGL2 complexed to PcSLN. siMCL1 complexed to PcSLN exerted the greatest in vitro anticancer effects in KB cells, followed by siMCL1 complexed to EcSLN, siGL2 complexed to PcSLN, PTX alone, and siMCL1 alone. In KB cell-xenografted mice, intratumoral injection of PcSLN complexed to siMCL1 significantly reduced the growth of tumors. Taken together, our results demonstrate the potential of cSLN for the development of co-delivery systems of various lipophilic anticancer drugs and therapeutic siRNAs.