Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates
We previously reported the synthesis of three DOX conjugates that represented different targeting vehicles and showed them to have antitumor activity both in vitro and in vivo. However, the relationships between the pharmacokinetics of these DOX conjugates and their chemical structures were not char...
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doaj-d2475cdea5b743e88c1edee3f4b03d992020-11-25T02:28:44ZengHindawi LimitedBioMed Research International2314-61332314-61412013-01-01201310.1155/2013/926584926584Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin ConjugatesMenglei Huan0Shuang Tian1Han Cui2Bangle Zhang3Dan Su4Jieping Wang5Kangchu Li6Weidong Cao7Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an, Shaan’xi 710032, ChinaDepartment of Obstetrics & Gynecology, PLA General Hospital, Beijing 100853, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an, Shaan’xi 710032, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an, Shaan’xi 710032, ChinaDepartment of Clinic Pharmacology, Wuhan General Hospital of Guangzhou Military Area Command, Wuhan, Hubei 430070, ChinaDepartment of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaan’xi 710038, ChinaDepartment of Radiation Medicine, School of Public Health, Fourth Military Medical University, Xi’an, Shaan’xi 710032, ChinaDepartment of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaan’xi 710032, ChinaWe previously reported the synthesis of three DOX conjugates that represented different targeting vehicles and showed them to have antitumor activity both in vitro and in vivo. However, the relationships between the pharmacokinetics of these DOX conjugates and their chemical structures were not characterized. In the current study, free DOX derived from each of the conjugates was found at low levels in the rat circulatory system, with conjugated DOX being the major form. The two polyethylene glycol (PEG) conjugates slowly released DOX, and t1/2β for total DOX from DOX-LNA, PEG-ami-DOX, and PEG-hyd-DOX was 5.79, 10.22, and 15.18 h, respectively. All three conjugates also deposited less DOX into normal organs than did an equivalent dose of free DOX, and the Cmax value of free DOX released by DOX- LNA, PEG-ami-DOX, and PEG-hyd-DOX was 32.5, 9.5, and 4.7 μg/g, respectively. Among the conjugates, the compound with an acid-labile bond between PEG and DOX exhibited the lowest free DOX deposition in healthy tissues, which should decrease the systemic toxicity of free DOX while allowing for tumor targeting by PEG.http://dx.doi.org/10.1155/2013/926584 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Menglei Huan Shuang Tian Han Cui Bangle Zhang Dan Su Jieping Wang Kangchu Li Weidong Cao |
spellingShingle |
Menglei Huan Shuang Tian Han Cui Bangle Zhang Dan Su Jieping Wang Kangchu Li Weidong Cao Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates BioMed Research International |
author_facet |
Menglei Huan Shuang Tian Han Cui Bangle Zhang Dan Su Jieping Wang Kangchu Li Weidong Cao |
author_sort |
Menglei Huan |
title |
Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates |
title_short |
Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates |
title_full |
Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates |
title_fullStr |
Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates |
title_full_unstemmed |
Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates |
title_sort |
deposition of doxorubicin in rats following administration of three newly synthesized doxorubicin conjugates |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2013-01-01 |
description |
We previously reported the synthesis of three DOX conjugates that represented different targeting vehicles and showed them to have antitumor activity both in vitro and in vivo. However, the relationships between the pharmacokinetics of these DOX conjugates and their chemical structures were not characterized. In the current study, free DOX derived from each of the conjugates was found at low levels in the rat circulatory system, with conjugated DOX being the major form. The two polyethylene glycol (PEG) conjugates slowly released DOX, and t1/2β for total DOX from DOX-LNA, PEG-ami-DOX, and PEG-hyd-DOX was 5.79, 10.22, and 15.18 h, respectively. All three conjugates also deposited less DOX into normal organs than did an equivalent dose of free DOX, and the Cmax value of free DOX released by DOX- LNA, PEG-ami-DOX, and PEG-hyd-DOX was 32.5, 9.5, and 4.7 μg/g, respectively. Among the conjugates, the compound with an acid-labile bond between PEG and DOX exhibited the lowest free DOX deposition in healthy tissues, which should decrease the systemic toxicity of free DOX while allowing for tumor targeting by PEG. |
url |
http://dx.doi.org/10.1155/2013/926584 |
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