Intra-tumoral injection of doxorubicin (Adriamycin) encapsulated in liposome inhibits tumor growth, prolongs survival time and is not associated with local or systemic side effects

Hitoshi Idani, Junji Matsuoka, Tatsuji Yasuda, Kazuko Kobayashi, Noriaki Tanaka

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Abstract

Encapsulation of doxorubicin (Adriamycin) in liposome (LipADM) augments the anti-tumor effects of the drug and reduces side effects such as cardiotoxicity. However, it does not always enhance anti-tumor effects because of entrapment by the reticuloendothelial system. In this study, we investigated the anti-tumor effect of LipADM injected directly into the tumor to augment tumor targeting. LipADM (7.5 mg/kg body weight), the same concentration as free ADM (FADM), was injected percutaneously or i.v. into 7-day-old established Meth-A tumors in mice. Mock liposome was injected percutaneously into tumors of control mice. Mean relative tumor weights of the 5 groups on day 15 were as follows: intra-tumoral injection of LipADM, 2.92 ± 1.09; intra-tumoral injection of FADM, 6.99 ± 2.92; i.v. injection of LipADM, 11.07 ± 7.95; i.v. injection of FADM, 11.80 ± 6.55; control, 23.94 ± 9.03. Mean survival times were as follows: intra-tumoral injection of LipADM, 46.2 ± 11.0 days; FADM, 34.6 ± 9.6 days; mock control, 30.2 ± 4.8 days. Histological examination showed no tissue damage at the site of s.c. injection of LipADM. ADM concentrations in tumor tissues after intra-tumoral injection were persistently high in the LipADM-treated group. Our results indicate that direct injection of LipADM into the tumor is therapeutically useful by producing persistently high concentrations of ADM in the target tissue, with few local and systemic side effects. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)645-651
Number of pages7
JournalInternational Journal of Cancer
Volume88
Issue number4
DOIs
Publication statusPublished - 2000

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Liposomes
Doxorubicin
Injections
Growth
Neoplasms
Mononuclear Phagocyte System
Tumor Burden
Drug-Related Side Effects and Adverse Reactions
Body Weight

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{43ee56b4f8fa4de3a2caaf34bc82b389,
title = "Intra-tumoral injection of doxorubicin (Adriamycin) encapsulated in liposome inhibits tumor growth, prolongs survival time and is not associated with local or systemic side effects",
abstract = "Encapsulation of doxorubicin (Adriamycin) in liposome (LipADM) augments the anti-tumor effects of the drug and reduces side effects such as cardiotoxicity. However, it does not always enhance anti-tumor effects because of entrapment by the reticuloendothelial system. In this study, we investigated the anti-tumor effect of LipADM injected directly into the tumor to augment tumor targeting. LipADM (7.5 mg/kg body weight), the same concentration as free ADM (FADM), was injected percutaneously or i.v. into 7-day-old established Meth-A tumors in mice. Mock liposome was injected percutaneously into tumors of control mice. Mean relative tumor weights of the 5 groups on day 15 were as follows: intra-tumoral injection of LipADM, 2.92 ± 1.09; intra-tumoral injection of FADM, 6.99 ± 2.92; i.v. injection of LipADM, 11.07 ± 7.95; i.v. injection of FADM, 11.80 ± 6.55; control, 23.94 ± 9.03. Mean survival times were as follows: intra-tumoral injection of LipADM, 46.2 ± 11.0 days; FADM, 34.6 ± 9.6 days; mock control, 30.2 ± 4.8 days. Histological examination showed no tissue damage at the site of s.c. injection of LipADM. ADM concentrations in tumor tissues after intra-tumoral injection were persistently high in the LipADM-treated group. Our results indicate that direct injection of LipADM into the tumor is therapeutically useful by producing persistently high concentrations of ADM in the target tissue, with few local and systemic side effects. (C) 2000 Wiley-Liss, Inc.",
author = "Hitoshi Idani and Junji Matsuoka and Tatsuji Yasuda and Kazuko Kobayashi and Noriaki Tanaka",
year = "2000",
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T1 - Intra-tumoral injection of doxorubicin (Adriamycin) encapsulated in liposome inhibits tumor growth, prolongs survival time and is not associated with local or systemic side effects

AU - Idani, Hitoshi

AU - Matsuoka, Junji

AU - Yasuda, Tatsuji

AU - Kobayashi, Kazuko

AU - Tanaka, Noriaki

PY - 2000

Y1 - 2000

N2 - Encapsulation of doxorubicin (Adriamycin) in liposome (LipADM) augments the anti-tumor effects of the drug and reduces side effects such as cardiotoxicity. However, it does not always enhance anti-tumor effects because of entrapment by the reticuloendothelial system. In this study, we investigated the anti-tumor effect of LipADM injected directly into the tumor to augment tumor targeting. LipADM (7.5 mg/kg body weight), the same concentration as free ADM (FADM), was injected percutaneously or i.v. into 7-day-old established Meth-A tumors in mice. Mock liposome was injected percutaneously into tumors of control mice. Mean relative tumor weights of the 5 groups on day 15 were as follows: intra-tumoral injection of LipADM, 2.92 ± 1.09; intra-tumoral injection of FADM, 6.99 ± 2.92; i.v. injection of LipADM, 11.07 ± 7.95; i.v. injection of FADM, 11.80 ± 6.55; control, 23.94 ± 9.03. Mean survival times were as follows: intra-tumoral injection of LipADM, 46.2 ± 11.0 days; FADM, 34.6 ± 9.6 days; mock control, 30.2 ± 4.8 days. Histological examination showed no tissue damage at the site of s.c. injection of LipADM. ADM concentrations in tumor tissues after intra-tumoral injection were persistently high in the LipADM-treated group. Our results indicate that direct injection of LipADM into the tumor is therapeutically useful by producing persistently high concentrations of ADM in the target tissue, with few local and systemic side effects. (C) 2000 Wiley-Liss, Inc.

AB - Encapsulation of doxorubicin (Adriamycin) in liposome (LipADM) augments the anti-tumor effects of the drug and reduces side effects such as cardiotoxicity. However, it does not always enhance anti-tumor effects because of entrapment by the reticuloendothelial system. In this study, we investigated the anti-tumor effect of LipADM injected directly into the tumor to augment tumor targeting. LipADM (7.5 mg/kg body weight), the same concentration as free ADM (FADM), was injected percutaneously or i.v. into 7-day-old established Meth-A tumors in mice. Mock liposome was injected percutaneously into tumors of control mice. Mean relative tumor weights of the 5 groups on day 15 were as follows: intra-tumoral injection of LipADM, 2.92 ± 1.09; intra-tumoral injection of FADM, 6.99 ± 2.92; i.v. injection of LipADM, 11.07 ± 7.95; i.v. injection of FADM, 11.80 ± 6.55; control, 23.94 ± 9.03. Mean survival times were as follows: intra-tumoral injection of LipADM, 46.2 ± 11.0 days; FADM, 34.6 ± 9.6 days; mock control, 30.2 ± 4.8 days. Histological examination showed no tissue damage at the site of s.c. injection of LipADM. ADM concentrations in tumor tissues after intra-tumoral injection were persistently high in the LipADM-treated group. Our results indicate that direct injection of LipADM into the tumor is therapeutically useful by producing persistently high concentrations of ADM in the target tissue, with few local and systemic side effects. (C) 2000 Wiley-Liss, Inc.

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