Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft

Anumita Chaudhury1, Surajit Das1, Ralph M Bunte2, Gigi NC Chiu11Department of Pharmacy, Faculty of Science, National University of Singapore, 2Duke-NUS Graduate Medical School, Singapore, Republic of SingaporeAbstract: Intraperitoneal (IP) therapy with platinum (Pt)-based drugs has shown promising r...

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Autores principales:	Bunte RM, Das S, Chaudhury A, Chiu GNC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d8255b1591334979a3f8c9fa4a1f5a46
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spelling	oai:doaj.org-article:d8255b1591334979a3f8c9fa4a1f5a462021-12-02T00:14:21ZPotent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft1176-91141178-2013https://doaj.org/article/d8255b1591334979a3f8c9fa4a1f5a462012-02-01T00:00:00Zhttp://www.dovepress.com/potent-therapeutic-activity-of-folate-receptor-targeted-liposomal-carb-a9260https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Anumita Chaudhury1, Surajit Das1, Ralph M Bunte2, Gigi NC Chiu11Department of Pharmacy, Faculty of Science, National University of Singapore, 2Duke-NUS Graduate Medical School, Singapore, Republic of SingaporeAbstract: Intraperitoneal (IP) therapy with platinum (Pt)-based drugs has shown promising results clinically; however, high locoregional concentration of the drug could lead to adverse side effects. In this study, IP administration was coupled with a folate receptor-targeted (FRT) liposomal system, in an attempt to achieve intracellular delivery of the Pt-based drug carboplatin in order to increase therapeutic efficacy and to minimize toxicity. In vitro and in vivo activity of FRT carboplatin liposomes was compared with the activity of free drug and nontargeted (NT) carboplatin liposomes using FR-overexpressing IGROV-1 ovarian cancer cells as the model. Significant reduction in cell viability was observed with FRT liposomes, which, compared with the free drug, provided an approximately twofold increase in carboplatin potency. The increase in drug potency was correlated with significantly higher cellular accumulation of Pt resulting from FRT liposomal delivery. Further evaluation was conducted in mice bearing intraperitoneally inoculated IGROV-1 ovarian tumor xenografts. A superior survival rate (five out of six animals) was achieved in animals treated with FRT carboplatin liposomes, injected intraperitoneally with a dose of 15 mg/kg and following a schedule of twice-weekly administration for 3 weeks. In contrast, no survivors were observed in the free drug or NT carboplatin liposome groups. The presence of cancer cells in lung and liver tissues was observed in the saline, free carboplatin, and NT carboplatin liposome groups. However, there was no sign of cancer cells or drug-related toxicity detected in tissues from the animals treated with FRT carboplatin liposomes. The results of this study have demonstrated for the first time that the approach of coupling IP administration with FRT liposomal delivery could provide significantly improved therapeutic efficacy of carboplatin in the treatment of metastatic ovarian cancer.Keywords: liposomes, ovarian cancer, targeted therapy, FRT carboplatin liposomesBunte RMDas SChaudhury AChiu GNCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 739-751 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Bunte RM Das S Chaudhury A Chiu GNC Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft
description	Anumita Chaudhury1, Surajit Das1, Ralph M Bunte2, Gigi NC Chiu11Department of Pharmacy, Faculty of Science, National University of Singapore, 2Duke-NUS Graduate Medical School, Singapore, Republic of SingaporeAbstract: Intraperitoneal (IP) therapy with platinum (Pt)-based drugs has shown promising results clinically; however, high locoregional concentration of the drug could lead to adverse side effects. In this study, IP administration was coupled with a folate receptor-targeted (FRT) liposomal system, in an attempt to achieve intracellular delivery of the Pt-based drug carboplatin in order to increase therapeutic efficacy and to minimize toxicity. In vitro and in vivo activity of FRT carboplatin liposomes was compared with the activity of free drug and nontargeted (NT) carboplatin liposomes using FR-overexpressing IGROV-1 ovarian cancer cells as the model. Significant reduction in cell viability was observed with FRT liposomes, which, compared with the free drug, provided an approximately twofold increase in carboplatin potency. The increase in drug potency was correlated with significantly higher cellular accumulation of Pt resulting from FRT liposomal delivery. Further evaluation was conducted in mice bearing intraperitoneally inoculated IGROV-1 ovarian tumor xenografts. A superior survival rate (five out of six animals) was achieved in animals treated with FRT carboplatin liposomes, injected intraperitoneally with a dose of 15 mg/kg and following a schedule of twice-weekly administration for 3 weeks. In contrast, no survivors were observed in the free drug or NT carboplatin liposome groups. The presence of cancer cells in lung and liver tissues was observed in the saline, free carboplatin, and NT carboplatin liposome groups. However, there was no sign of cancer cells or drug-related toxicity detected in tissues from the animals treated with FRT carboplatin liposomes. The results of this study have demonstrated for the first time that the approach of coupling IP administration with FRT liposomal delivery could provide significantly improved therapeutic efficacy of carboplatin in the treatment of metastatic ovarian cancer.Keywords: liposomes, ovarian cancer, targeted therapy, FRT carboplatin liposomes
format	article
author	Bunte RM Das S Chaudhury A Chiu GNC
author_facet	Bunte RM Das S Chaudhury A Chiu GNC
author_sort	Bunte RM
title	Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft
title_short	Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft
title_full	Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft
title_fullStr	Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft
title_full_unstemmed	Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft
title_sort	potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/d8255b1591334979a3f8c9fa4a1f5a46
work_keys_str_mv	AT bunterm potenttherapeuticactivityoffolatereceptortargetedliposomalcarboplatininthelocalizedtreatmentofintraperitoneallygrownhumanovariantumorxenograft AT dass potenttherapeuticactivityoffolatereceptortargetedliposomalcarboplatininthelocalizedtreatmentofintraperitoneallygrownhumanovariantumorxenograft AT chaudhurya potenttherapeuticactivityoffolatereceptortargetedliposomalcarboplatininthelocalizedtreatmentofintraperitoneallygrownhumanovariantumorxenograft AT chiugnc potenttherapeuticactivityoffolatereceptortargetedliposomalcarboplatininthelocalizedtreatmentofintraperitoneallygrownhumanovariantumorxenograft
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Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft

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