TY - JOUR
T1 - Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug
AU - Garbuzenko, Olga B.
AU - Saad, Maha
AU - Betigeri, Seema
AU - Zhang, Min
AU - Vetcher, Alexandre A.
AU - Soldatenkov, Viatcheslav A.
AU - Reimer, David C.
AU - Pozharov, Vitaly P.
AU - Minko, Tamara
N1 - Funding Information:
The research was supported in part by NIH grants CA100098, CA111766, and CA074145 from the National Cancer Institute and by a LCD-23812-N grant from the American Lung Association of New Jersey.
PY - 2009/2
Y1 - 2009/2
N2 - Purpose.To compare systemic intravenous and local intratracheal delivery of doxorubicin (DOX), antisense oligonucleotides (ASO) and small interfering RNA (siRNA). Methods. "Neutral" and cationic liposomes were used to deliver DOX, ASO, and siRNA. Liposomes were characterized by dynamic light scattering, zeta-potential, and atomic force microscopy. Cellular internalization of DOX, ASO and siRNA was studied by confocal microscopy on human lung carcinoma cells. In vivo experiments were carried out on nude mice with an orthotopic model of human lung cancer. Results. Liposomes provided for an efficient intracellular delivery of DOX, ASO, and siRNA in vitro. Intratracheal delivery of both types of liposomes in vivo led to higher peak concentrations and much longer retention of liposomes, DOX, ASO and siRNA in the lungs when compared with systemic administration. It was found that local intratracheal treatment of lung cancer with liposomal DOX was more efficient when compared with free and liposomal DOX delivered intravenously. Conclusions. The present study outlined the clear advantages of local intratracheal delivery of liposomal drugs for the treatment of lung cancer when compared with systemic administration of the same drug.
AB - Purpose.To compare systemic intravenous and local intratracheal delivery of doxorubicin (DOX), antisense oligonucleotides (ASO) and small interfering RNA (siRNA). Methods. "Neutral" and cationic liposomes were used to deliver DOX, ASO, and siRNA. Liposomes were characterized by dynamic light scattering, zeta-potential, and atomic force microscopy. Cellular internalization of DOX, ASO and siRNA was studied by confocal microscopy on human lung carcinoma cells. In vivo experiments were carried out on nude mice with an orthotopic model of human lung cancer. Results. Liposomes provided for an efficient intracellular delivery of DOX, ASO, and siRNA in vitro. Intratracheal delivery of both types of liposomes in vivo led to higher peak concentrations and much longer retention of liposomes, DOX, ASO and siRNA in the lungs when compared with systemic administration. It was found that local intratracheal treatment of lung cancer with liposomal DOX was more efficient when compared with free and liposomal DOX delivered intravenously. Conclusions. The present study outlined the clear advantages of local intratracheal delivery of liposomal drugs for the treatment of lung cancer when compared with systemic administration of the same drug.
KW - Antisense oligonucleotides
KW - Imaging
KW - Liposomes
KW - Local lung delivery of siRNA
KW - Lung cancer
KW - Pulmonary delivery
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U2 - 10.1007/s11095-008-9755-4
DO - 10.1007/s11095-008-9755-4
M3 - Article
C2 - 18958402
AN - SCOPUS:58549093528
SN - 0724-8741
VL - 26
SP - 382
EP - 394
JO - Pharmaceutical research
JF - Pharmaceutical research
IS - 2
ER -