Pharmacokinetics and Disposition of a Localized Lymphatic Polymeric Hyaluronan Conjugate of Cisplatin in Rodents
dc.contributor.author | Cai, Shuang | |
dc.contributor.author | Xie, Yumei | |
dc.contributor.author | Davies, Neal M. | |
dc.contributor.author | Cohen, Mark S. | |
dc.contributor.author | Forrest, M. Laird | |
dc.date.accessioned | 2017-04-26T15:59:32Z | |
dc.date.available | 2017-04-26T15:59:32Z | |
dc.date.issued | 2010-06 | |
dc.identifier.citation | Cai, S., Xie, Y., Davies, N. M., Cohen, M. S., & Forrest, M. L. (2010). Pharmacokinetics and Disposition of a Localized Lymphatic Polymeric Hyaluronan Conjugate of Cisplatin in Rodents. Journal of Pharmaceutical Sciences, 99(6), 2664–2671. http://doi.org/10.1002/jps.22016 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23783 | |
dc.description.abstract | 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. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Cancer Chemotherapy | en_US |
dc.subject | Pharmacokinetics | en_US |
dc.subject | Biodegradable polymers | en_US |
dc.subject | Controlled release | en_US |
dc.subject | Lymphatic transport | en_US |
dc.subject | Polymeric drug carrier | en_US |
dc.subject | Polymeric drug delivery systems | en_US |
dc.title | Pharmacokinetics and Disposition of a Localized Lymphatic Polymeric Hyaluronan Conjugate of Cisplatin in Rodents | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Cai, Shuang | |
kusw.kuauthor | Xie, Yumei | |
kusw.kuauthor | Forrest, M. Laird | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1002/jps.22016 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC3102643 | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.