Thermochemotherapy: Synergism between hyperthermia and liposomal bleomycin in mice bearing melanoma B16F1

S.B. Tiwari, V.N. Udupa, S. Rao, P.U Devi

Research output: Contribution to journalArticle

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Abstract

This study was aimed at enhancing the antitumour efficacy of bleomycin by encapsulating it in temperature-sensitive liposomes and using it in combination with localized hyperthermia of tumours for targeted delivery. Large unilammelar vesicles (LUV) made of synthetic lipids (disteroyl phosphatidylcholine and dipalmitoyl phosphatidylcholine) showing gel-to- liquid phase transition at 41°C, were used to encapsulate bleomycin. Comparison of Luv when incubated in saline at various temperatures revealed that maximum drug release (80%) occurred at 42°C compared with less than 5% release at 37°C. Better stability during storage was also observed with thermosensitive bleomycin liposomes. When administered intravenously to C57BL/6J mice bearing melanoma B16F1 tumour at 10 mg kg-1 dose, liposomal bleomycin in combination with hyperthermia (43°C, 30 min or 1 h) exhibited improved anticancer activity as evident by the enhanced volume doubling time and growth delay compared with animals treated with an equivalent dose of free bleomycin with or without hyperthermia. The results suggest that hyperthermia in combination with bleomycin encapsulated in temperature sensitive liposomes may be a useful targeted drug delivery system for more effective management of melanoma B16F1.
Original languageEnglish
Pages (from-to)19-23
Number of pages5
JournalPharmacy and Pharmacology Communications
Volume6
Issue number1
Publication statusPublished - 2000

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Bleomycin
Melanoma
Fever
Liposomes
Temperature
1,2-Dipalmitoylphosphatidylcholine
Phase Transition
Drug Delivery Systems
Phosphatidylcholines
Inbred C57BL Mouse
Neoplasms
Gels
Lipids
indium-bleomycin
Growth

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@article{172a12fee7d846549d06ac867c228ed0,
title = "Thermochemotherapy: Synergism between hyperthermia and liposomal bleomycin in mice bearing melanoma B16F1",
abstract = "This study was aimed at enhancing the antitumour efficacy of bleomycin by encapsulating it in temperature-sensitive liposomes and using it in combination with localized hyperthermia of tumours for targeted delivery. Large unilammelar vesicles (LUV) made of synthetic lipids (disteroyl phosphatidylcholine and dipalmitoyl phosphatidylcholine) showing gel-to- liquid phase transition at 41°C, were used to encapsulate bleomycin. Comparison of Luv when incubated in saline at various temperatures revealed that maximum drug release (80{\%}) occurred at 42°C compared with less than 5{\%} release at 37°C. Better stability during storage was also observed with thermosensitive bleomycin liposomes. When administered intravenously to C57BL/6J mice bearing melanoma B16F1 tumour at 10 mg kg-1 dose, liposomal bleomycin in combination with hyperthermia (43°C, 30 min or 1 h) exhibited improved anticancer activity as evident by the enhanced volume doubling time and growth delay compared with animals treated with an equivalent dose of free bleomycin with or without hyperthermia. The results suggest that hyperthermia in combination with bleomycin encapsulated in temperature sensitive liposomes may be a useful targeted drug delivery system for more effective management of melanoma B16F1.",
author = "S.B. Tiwari and V.N. Udupa and S. Rao and P.U Devi",
note = "Export Date: 10 November 2017 CODEN: PPCOF Correspondence Address: Udupa, V.N.; Department of Pharmaceutics, College of Pharmaceutical Sciences, Manipal 576 119, India; email: info@mahe.ernet.in Chemicals/CAS: bleomycin, 11056-06-7; dipalmitoylphosphatidylcholine, 2644-64-6; distearoylphosphatidylcholine, 4539-70-2 Tradenames: bleocin, Khandelwal Laboratories, India Manufacturers: Khandelwal Laboratories, India; Sigma, United States References: Bassett, J.B., Anderson, R.U., Tacker, J.R., Use of temperature sensitive liposomes in the selective delivery of methotrexate and cis-platinum analogues to murine bladder tumour (1986) J. Urology, 135, pp. 612-615; Gregoriadis, G., (1988) Liposomes as Drug Carriers: Recent Trends and Progress, pp. 189-325. , John Wiley & Sons, Chichester; Gregoriadis, G., Neerunjun, D.E., Homing of liposomes to target cells (1975) Biochem. Biophys. Res. Commun., 65, pp. 537-544; Gregoriadis, G., Ryman, B.E., Lysosomal localisation of β-fructofuranoside containing liposomes injected into rats (1972) Biochem. J., 129, pp. 123-133; Hahn, G.M., Potential for therapy of drugs and hyperthermia (1979) Cancer Res., 39, pp. 2264-2268; Hahn, G.M., Braun, J., Har-Kedar, I., Thermochemotherapy: Synergism between hyperthermia (42-43°C) and adriamycin (or bleomycin) in mammalian cell inactivation (1975) Proc. Natl Acad. Sci. USA, 72, pp. 937-940; Iga, K., Hamaguchi, N., Igari, Y., Ogawa, Y., Toguchi, H., Shimamoto, T., Increased tumor cisplatin levels in heated tumors in mice after administration of thermosensitive large unilamellar vesicles encapsulating cisplatin (1991) J. Pharm. Sci., 80, pp. 522-525; Juliano, R.L., Stamp, D., Lectin mediated attachment glycoprotein bearing liposomes to cells (1976) Nature, 261, pp. 235-238; Marmor, B., Actions of hyperthermia and chemotherapy in animals (1979) Cancer Res., 39, pp. 2269-2276; Raja Naresh, R.A., Udupa, N., Niosome encapsulated bleomycin (1996) S.T.P. Pharma Sci., 6, pp. 61-71; Sorensen, E.N., Weisman, G., Vidaver, G.A., A sephadex column for measuring uptake and loss of low molecular weight solutes from small lipid rich vesicles (1977) Anal. Biochem., 82, pp. 376-384; Szoka, F., Papahadjopoulus, D., Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse phase evaporation (1978) Proc. Natl Acad. Sci. USA, 75, pp. 4194-4198; Szoka, F., Papahadjopoulus, D., Comparative properties and methods of preparation of lipid vesicles (liposomes) (1980) Ann. Rev. Biophys. Bioeng., 9, pp. 467-508; Tacker, J.R., Anderson, R.U., Delivery of antitumor drug to bladder cancer by use of phase transition liposomes and hyperthermia (1982) J. Urology, 127, pp. 1211-1214; Uma Devi, P., Rao, B.S.S., Response of mouse sarcoma-180 to bleomycin in combination with radiation and hyperthermia (1993) Strahlenther. Onkol., 169, pp. 601-607; Weinstein, J.N., Magin, R.L., Cysyk, R.L., Zaharko, D.S., Treatment of solid L1210 murine tumors with local hyperthermia and temperature-sensitive liposomes containing methotrexate (1980) Cancer Res., 40, pp. 1388-1395; Wu, D.E., Zheng, Z., Quin, Y., Keng, P., Sutherland, R.M., Lasanga, L., The interaction between bleomycin and irradiation on cell survival and DNA damage in mammalian cell cultures (1985) J. Radiat. Oncol. Phys., 11, pp. 2125-2131; Yatvin, M.B., Weinstein, J.N., Dennis, W.H., Bluementhal, R., Design of liposomes for enhanced local release of drugs by hyperthermia (1978) Science, 202, pp. 1290-1293; Yatvin, M.B., Muhlensiepen, H., Porschen, W., Weinstein, J.N., Feinendegen, L.E., Selective delivery of liposomes associated cis-dichlorodiammineplatinum (II) by heat and its influence on tumour drug uptake and growth (1981) Cancer Res., 41, pp. 1602-1607",
year = "2000",
language = "English",
volume = "6",
pages = "19--23",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Pharmaceutical Press",
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Thermochemotherapy: Synergism between hyperthermia and liposomal bleomycin in mice bearing melanoma B16F1. / Tiwari, S.B.; Udupa, V.N.; Rao, S.; Devi, P.U.

In: Pharmacy and Pharmacology Communications, Vol. 6, No. 1, 2000, p. 19-23.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thermochemotherapy: Synergism between hyperthermia and liposomal bleomycin in mice bearing melanoma B16F1

AU - Tiwari, S.B.

AU - Udupa, V.N.

AU - Rao, S.

AU - Devi, P.U

N1 - Export Date: 10 November 2017 CODEN: PPCOF Correspondence Address: Udupa, V.N.; Department of Pharmaceutics, College of Pharmaceutical Sciences, Manipal 576 119, India; email: info@mahe.ernet.in Chemicals/CAS: bleomycin, 11056-06-7; dipalmitoylphosphatidylcholine, 2644-64-6; distearoylphosphatidylcholine, 4539-70-2 Tradenames: bleocin, Khandelwal Laboratories, India Manufacturers: Khandelwal Laboratories, India; Sigma, United States References: Bassett, J.B., Anderson, R.U., Tacker, J.R., Use of temperature sensitive liposomes in the selective delivery of methotrexate and cis-platinum analogues to murine bladder tumour (1986) J. Urology, 135, pp. 612-615; Gregoriadis, G., (1988) Liposomes as Drug Carriers: Recent Trends and Progress, pp. 189-325. , John Wiley & Sons, Chichester; Gregoriadis, G., Neerunjun, D.E., Homing of liposomes to target cells (1975) Biochem. Biophys. Res. Commun., 65, pp. 537-544; Gregoriadis, G., Ryman, B.E., Lysosomal localisation of β-fructofuranoside containing liposomes injected into rats (1972) Biochem. J., 129, pp. 123-133; Hahn, G.M., Potential for therapy of drugs and hyperthermia (1979) Cancer Res., 39, pp. 2264-2268; Hahn, G.M., Braun, J., Har-Kedar, I., Thermochemotherapy: Synergism between hyperthermia (42-43°C) and adriamycin (or bleomycin) in mammalian cell inactivation (1975) Proc. Natl Acad. Sci. USA, 72, pp. 937-940; Iga, K., Hamaguchi, N., Igari, Y., Ogawa, Y., Toguchi, H., Shimamoto, T., Increased tumor cisplatin levels in heated tumors in mice after administration of thermosensitive large unilamellar vesicles encapsulating cisplatin (1991) J. Pharm. Sci., 80, pp. 522-525; Juliano, R.L., Stamp, D., Lectin mediated attachment glycoprotein bearing liposomes to cells (1976) Nature, 261, pp. 235-238; Marmor, B., Actions of hyperthermia and chemotherapy in animals (1979) Cancer Res., 39, pp. 2269-2276; Raja Naresh, R.A., Udupa, N., Niosome encapsulated bleomycin (1996) S.T.P. Pharma Sci., 6, pp. 61-71; Sorensen, E.N., Weisman, G., Vidaver, G.A., A sephadex column for measuring uptake and loss of low molecular weight solutes from small lipid rich vesicles (1977) Anal. Biochem., 82, pp. 376-384; Szoka, F., Papahadjopoulus, D., Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse phase evaporation (1978) Proc. Natl Acad. Sci. USA, 75, pp. 4194-4198; Szoka, F., Papahadjopoulus, D., Comparative properties and methods of preparation of lipid vesicles (liposomes) (1980) Ann. Rev. Biophys. Bioeng., 9, pp. 467-508; Tacker, J.R., Anderson, R.U., Delivery of antitumor drug to bladder cancer by use of phase transition liposomes and hyperthermia (1982) J. Urology, 127, pp. 1211-1214; Uma Devi, P., Rao, B.S.S., Response of mouse sarcoma-180 to bleomycin in combination with radiation and hyperthermia (1993) Strahlenther. Onkol., 169, pp. 601-607; Weinstein, J.N., Magin, R.L., Cysyk, R.L., Zaharko, D.S., Treatment of solid L1210 murine tumors with local hyperthermia and temperature-sensitive liposomes containing methotrexate (1980) Cancer Res., 40, pp. 1388-1395; Wu, D.E., Zheng, Z., Quin, Y., Keng, P., Sutherland, R.M., Lasanga, L., The interaction between bleomycin and irradiation on cell survival and DNA damage in mammalian cell cultures (1985) J. Radiat. Oncol. Phys., 11, pp. 2125-2131; Yatvin, M.B., Weinstein, J.N., Dennis, W.H., Bluementhal, R., Design of liposomes for enhanced local release of drugs by hyperthermia (1978) Science, 202, pp. 1290-1293; Yatvin, M.B., Muhlensiepen, H., Porschen, W., Weinstein, J.N., Feinendegen, L.E., Selective delivery of liposomes associated cis-dichlorodiammineplatinum (II) by heat and its influence on tumour drug uptake and growth (1981) Cancer Res., 41, pp. 1602-1607

PY - 2000

Y1 - 2000

N2 - This study was aimed at enhancing the antitumour efficacy of bleomycin by encapsulating it in temperature-sensitive liposomes and using it in combination with localized hyperthermia of tumours for targeted delivery. Large unilammelar vesicles (LUV) made of synthetic lipids (disteroyl phosphatidylcholine and dipalmitoyl phosphatidylcholine) showing gel-to- liquid phase transition at 41°C, were used to encapsulate bleomycin. Comparison of Luv when incubated in saline at various temperatures revealed that maximum drug release (80%) occurred at 42°C compared with less than 5% release at 37°C. Better stability during storage was also observed with thermosensitive bleomycin liposomes. When administered intravenously to C57BL/6J mice bearing melanoma B16F1 tumour at 10 mg kg-1 dose, liposomal bleomycin in combination with hyperthermia (43°C, 30 min or 1 h) exhibited improved anticancer activity as evident by the enhanced volume doubling time and growth delay compared with animals treated with an equivalent dose of free bleomycin with or without hyperthermia. The results suggest that hyperthermia in combination with bleomycin encapsulated in temperature sensitive liposomes may be a useful targeted drug delivery system for more effective management of melanoma B16F1.

AB - This study was aimed at enhancing the antitumour efficacy of bleomycin by encapsulating it in temperature-sensitive liposomes and using it in combination with localized hyperthermia of tumours for targeted delivery. Large unilammelar vesicles (LUV) made of synthetic lipids (disteroyl phosphatidylcholine and dipalmitoyl phosphatidylcholine) showing gel-to- liquid phase transition at 41°C, were used to encapsulate bleomycin. Comparison of Luv when incubated in saline at various temperatures revealed that maximum drug release (80%) occurred at 42°C compared with less than 5% release at 37°C. Better stability during storage was also observed with thermosensitive bleomycin liposomes. When administered intravenously to C57BL/6J mice bearing melanoma B16F1 tumour at 10 mg kg-1 dose, liposomal bleomycin in combination with hyperthermia (43°C, 30 min or 1 h) exhibited improved anticancer activity as evident by the enhanced volume doubling time and growth delay compared with animals treated with an equivalent dose of free bleomycin with or without hyperthermia. The results suggest that hyperthermia in combination with bleomycin encapsulated in temperature sensitive liposomes may be a useful targeted drug delivery system for more effective management of melanoma B16F1.

M3 - Article

VL - 6

SP - 19

EP - 23

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 1

ER -