Pharmacokinetics and disposition of a localized lymphatic polymeric hyaluronan conjugate of cisplatin in rodents.
Pharmacokinetics and disposition of a localized lymphatic polymeric hyaluronan conjugate of cisplatin in rodents.
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DOI：
10.1002/jps.22016
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发表时间：
2010-06
影响因子：
3.8
通讯作者：
Forrest, M. Laird
中科院分区：
文献类型：
--
作者：
Cai, Shuang;Xie, Yumei;Davies, Neal M.;Cohen, Mark S.;Forrest, M. Laird
关键词：
Cisplatin (CDDP) is an effective anticancer agent for many solid tumors but has significant systemic toxicity limiting its use in many patients. We have designed a loco-regional delivery system to increase platinum levels in the lymphatics, where early metastasis is most likely to occur, while reducing systemic toxicities. CDDP was conjugated to a biocompatible polymer hyaluronan (HA), with a conjugation degree of approximately 20% (w/w). Conjugates were delivered via subcutaneous injection into the mammary fat pad of rats. Intravenous hyaluronan–cisplatin (HA–Pt) exhibited an increased plasma area under the curve (AUC) 2.7-fold compared to conventional CDDP but with a reduced peak plasma level (Cmax), and HA–Pt increased the ipsilateral lymph node AUC by 3.8-fold compared to CDDP. Urine creatinine was unchanged over 30 days following dosing of HA–Pt. This study demonstrates that intralymphatic drug delivery with polymer-conjugated platinum may provide greater tissue and systemic plasma concentrations of platinum than intravenous CDDP. In addition, localized particle delivery augmented distribution in the loco-regional tissue basin where tumor burden predominates, while renal toxicity compared to standard intravenous CDDP was significantly reduced.
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影响因子：
8.8
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.2
作者：
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Forrest, M. Laird
影响因子：
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DOI：
10.1097/01.asn.0000042803.28024.92
发表时间：
2003-01-01
影响因子：
13.6
作者：
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