Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug

Olga B. Garbuzenko, Maha Saad, Seema Betigeri, Min Zhang, Alexandre A. Vetcher, Viatcheslav A. Soldatenkov, David C. Reimer, Vitaly P. Pozharov, Tamara Minko

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)382-394
Number of pages13
JournalPharmaceutical research
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2009

Fingerprint

Antisense Oligonucleotides
Liposomes
Doxorubicin
Small Interfering RNA
Lung Neoplasms
Pharmaceutical Preparations
Lung
Confocal microscopy
Atomic Force Microscopy
Dynamic light scattering
Zeta potential
Nude Mice
Confocal Microscopy
Atomic force microscopy
Cells
Carcinoma
Therapeutics
Experiments
liposomal doxorubicin

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Molecular Medicine
  • Biotechnology
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Keywords

  • Antisense oligonucleotides
  • Imaging
  • Liposomes
  • Local lung delivery of siRNA
  • Lung cancer
  • Pulmonary delivery

Cite this

Garbuzenko, Olga B. ; Saad, Maha ; Betigeri, Seema ; Zhang, Min ; Vetcher, Alexandre A. ; Soldatenkov, Viatcheslav A. ; Reimer, David C. ; Pozharov, Vitaly P. ; Minko, Tamara. / Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug. In: Pharmaceutical research. 2009 ; Vol. 26, No. 2. pp. 382-394.
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Garbuzenko, OB, Saad, M, Betigeri, S, Zhang, M, Vetcher, AA, Soldatenkov, VA, Reimer, DC, Pozharov, VP & Minko, T 2009, 'Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug', Pharmaceutical research, vol. 26, no. 2, pp. 382-394. https://doi.org/10.1007/s11095-008-9755-4

Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug. / Garbuzenko, Olga B.; Saad, Maha; Betigeri, Seema; Zhang, Min; Vetcher, Alexandre A.; Soldatenkov, Viatcheslav A.; Reimer, David C.; Pozharov, Vitaly P.; Minko, Tamara.

In: Pharmaceutical research, Vol. 26, No. 2, 01.02.2009, p. 382-394.

Research output: Contribution to journalArticle

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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

PY - 2009/2/1

Y1 - 2009/2/1

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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