Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo
Lulu Cai,1,3,† Xianhuo Wang,4,† Wenwen Wang,1,† Neng Qiu,1 Jiaolin Wen,1 Xingmei Duan,1 Xia Li,1 Xiang Chen,1 Li Yang,1 Zhiyong Qian,1 Yuquan Wei,1 Lijuan Chen,1,2 1State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichua...
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Dove Medical Press
2012
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oai:doaj.org-article:4b8c048b2ffd437791b200730f71e1e52021-12-02T02:28:08ZPeptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo1176-91141178-2013https://doaj.org/article/4b8c048b2ffd437791b200730f71e1e52012-08-01T00:00:00Zhttp://www.dovepress.com/peptide-ligand-and-peg-mediated-long-circulating-liposome-targeted-to--a10689https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Lulu Cai,1,3,† Xianhuo Wang,4,† Wenwen Wang,1,† Neng Qiu,1 Jiaolin Wen,1 Xingmei Duan,1 Xia Li,1 Xiang Chen,1 Li Yang,1 Zhiyong Qian,1 Yuquan Wei,1 Lijuan Chen,1,2 1State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, 2State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 3Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Sichuan Chengdu, China; 4Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China†These authors equally contributed to this researchBackground and methods: Paclitaxel, a widely used antitumor agent, has limited clinical application due to its hydrophobicity and systemic toxicity. To achieve sustained and targeted delivery of paclitaxel to tumor sites, liposomes composed of egg phosphatidylcholine, cholesterol, and distearolyphosphatidyl ethanolamine-N-poly(ethylene glycol) (PEG2000) were prepared by a lipid film method. In addition, the liposomes also contained truncated fibroblast growth factor fragment-PEG-cholesterol as a ligand targeting the tumor marker fibroblast growth factor receptor. Physicochemical characteristics, such as particle size, zeta potential, entrapment efficiency, and release profiles were investigated. Pharmacokinetics and biodistribution were evaluated in C57BL/6 J mice bearing B16 melanoma after intravenous injection of paclitaxel formulated in Cremophor EL (free paclitaxel), conventional liposomes (CL-PTX), or in targeted PEGylated liposomes (TL-PTX).Results: Compared with CL-PTX and free paclitaxel, TL-PTX prolonged the half-life of paclitaxel by 2.01-fold and 3.40-fold, respectively, in plasma and improved the AUC0→t values of paclitaxel by 1.56-fold and 2.31-fold, respectively, in blood. Biodistribution studies showed high accumulation of TL-PTX in tumor tissue and organs containing the mononuclear phagocyte system (liver and spleen), but a considerable decrease in other organs (heart, lung, and kidney) compared with CL-PTX and free paclitaxel.Conclusion: The truncated fibroblast growth factor fragment-conjugated PEGylated liposome has promising potential as a long-circulating and tumor-targeting carrier system.Keywords: paclitaxel, truncated fibroblast growth factor fragment, poly(ethylene glycol), liposomes, targeted drug deliveryCai LWang XWang WQiu NWen JDuan XLi XChen XYang LQian ZWei YChen LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4499-4510 (2012) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Cai L Wang X Wang W Qiu N Wen J Duan X Li X Chen X Yang L Qian Z Wei Y Chen L Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo |
| description |
Lulu Cai,1,3,† Xianhuo Wang,4,† Wenwen Wang,1,† Neng Qiu,1 Jiaolin Wen,1 Xingmei Duan,1 Xia Li,1 Xiang Chen,1 Li Yang,1 Zhiyong Qian,1 Yuquan Wei,1 Lijuan Chen,1,2 1State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, 2State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 3Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Sichuan Chengdu, China; 4Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China†These authors equally contributed to this researchBackground and methods: Paclitaxel, a widely used antitumor agent, has limited clinical application due to its hydrophobicity and systemic toxicity. To achieve sustained and targeted delivery of paclitaxel to tumor sites, liposomes composed of egg phosphatidylcholine, cholesterol, and distearolyphosphatidyl ethanolamine-N-poly(ethylene glycol) (PEG2000) were prepared by a lipid film method. In addition, the liposomes also contained truncated fibroblast growth factor fragment-PEG-cholesterol as a ligand targeting the tumor marker fibroblast growth factor receptor. Physicochemical characteristics, such as particle size, zeta potential, entrapment efficiency, and release profiles were investigated. Pharmacokinetics and biodistribution were evaluated in C57BL/6 J mice bearing B16 melanoma after intravenous injection of paclitaxel formulated in Cremophor EL (free paclitaxel), conventional liposomes (CL-PTX), or in targeted PEGylated liposomes (TL-PTX).Results: Compared with CL-PTX and free paclitaxel, TL-PTX prolonged the half-life of paclitaxel by 2.01-fold and 3.40-fold, respectively, in plasma and improved the AUC0→t values of paclitaxel by 1.56-fold and 2.31-fold, respectively, in blood. Biodistribution studies showed high accumulation of TL-PTX in tumor tissue and organs containing the mononuclear phagocyte system (liver and spleen), but a considerable decrease in other organs (heart, lung, and kidney) compared with CL-PTX and free paclitaxel.Conclusion: The truncated fibroblast growth factor fragment-conjugated PEGylated liposome has promising potential as a long-circulating and tumor-targeting carrier system.Keywords: paclitaxel, truncated fibroblast growth factor fragment, poly(ethylene glycol), liposomes, targeted drug delivery |
| format |
article |
| author |
Cai L Wang X Wang W Qiu N Wen J Duan X Li X Chen X Yang L Qian Z Wei Y Chen L |
| author_facet |
Cai L Wang X Wang W Qiu N Wen J Duan X Li X Chen X Yang L Qian Z Wei Y Chen L |
| author_sort |
Cai L |
| title |
Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo |
| title_short |
Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo |
| title_full |
Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo |
| title_fullStr |
Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo |
| title_full_unstemmed |
Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo |
| title_sort |
peptide ligand and peg-mediated long-circulating liposome targeted to fgfr overexpressing tumor in vivo |
| publisher |
Dove Medical Press |
| publishDate |
2012 |
| url |
https://doaj.org/article/4b8c048b2ffd437791b200730f71e1e5 |
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