Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 268-273 |
| Number of pages | 6 |
| Journal | European Journal of Pharmaceutics and Biopharmaceutics |
| Volume | 80 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2012 Feb 1 |
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Keywords
- Co-delivery
- Combined cancer therapy
- Paclitaxel
- SiRNA
- Solid lipid nanoparticles
ASJC Scopus subject areas
- Biotechnology
- Pharmaceutical Science
Cite this
Cationic solid lipid nanoparticles for co-delivery of paclitaxel and siRNA. / Yu, Yong Hee; Kim, Eunjoong; Park, Dai Eui; Shim, Gayong; Lee, Sangbin; Kim, Young Bong; Kim, Chan Wha; Oh, Yu Kyoung.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 80, No. 2, 01.02.2012, p. 268-273.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cationic solid lipid nanoparticles for co-delivery of paclitaxel and siRNA
AU - Yu, Yong Hee
AU - Kim, Eunjoong
AU - Park, Dai Eui
AU - Shim, Gayong
AU - Lee, Sangbin
AU - Kim, Young Bong
AU - Kim, Chan Wha
AU - Oh, Yu Kyoung
PY - 2012/2/1
Y1 - 2012/2/1
N2 - 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.
AB - 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.
KW - Co-delivery
KW - Combined cancer therapy
KW - Paclitaxel
KW - SiRNA
KW - Solid lipid nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=84856619472&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856619472&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2011.11.002
DO - 10.1016/j.ejpb.2011.11.002
M3 - Article
C2 - 22108492
AN - SCOPUS:84856619472
VL - 80
SP - 268
EP - 273
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
IS - 2
ER -