Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug.
OBJECTIVE
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.
Garbuzenko
Olga B
OB
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854-8020, USA.
Saad
Maha
M
Betigeri
Seema
S
Zhang
Min
M
Vetcher
Alexandre A
AA
Soldatenkov
Viatcheslav A
VA
Reimer
David C
DC
Pozharov
Vitaly P
VP
Minko
Tamara
T
D000280:Administration, Inhalation; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007275:Injections, Intravenous; D008027:Light; D008081:Liposomes; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012542:Scattering, Radiation; D013499:Surface Properties; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; D004317:Doxorubicin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane