Preclinical evaluation of injectable sirolimus formulated with polymeric nanoparticle for cancer therapy
Ha Na Woo1*, Hye Kyung Chung2*, Eun Jin Ju1, Joohee Jung1,3, Hye-Won Kang4, Sa-Won Lee4, Min-Hyo Seo4, Jin Seong Lee5, Jung Shin Lee1,6, Heon Joo Park7, Si Yeol Song1,8, Seong-Yun Jeong1, Eun Kyung Choi1,2,81Institute for Innovative Cancer Research, 2Center for Development and Commercialization of A...
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| Autores principales: | , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2012
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| Acceso en línea: | https://doaj.org/article/7e101255baee40b5b2876380e6038d5c |
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| Sumario: | Ha Na Woo1*, Hye Kyung Chung2*, Eun Jin Ju1, Joohee Jung1,3, Hye-Won Kang4, Sa-Won Lee4, Min-Hyo Seo4, Jin Seong Lee5, Jung Shin Lee1,6, Heon Joo Park7, Si Yeol Song1,8, Seong-Yun Jeong1, Eun Kyung Choi1,2,81Institute for Innovative Cancer Research, 2Center for Development and Commercialization of Anti-cancer Therapeutics, Asan Medical Center, Seoul, 3College of Pharmacy, Duksung Women's University, Seoul, 4Department of Parenteral Delivery Program, Samyang Pharmaceuticals R&D, Daejeon, 5Department of Radiology and Research Institute of Radiology, 6Department of Internal Medicine, Asan Medical Center, Seoul, 7Department of Microbiology, College of Medicine, Inha University, Inchon, 8Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea*These authors contributed equally to this studyAbstract: Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of sirolimus for human cancer treatment. Polymeric nanoparticle (PNP)–sirolimus was developed as an injectable formulation and has been characterized by transmission electron microscopy and dynamic light scattering. Pharmacokinetic analysis revealed that PNP–sirolimus has prolonged circulation in the blood. In addition, PNP–sirolimus preserved the in vitro killing effect of free sirolimus against cancer cells, and intravenous administration displayed its potent in vivo anticancer efficacy in xenograft tumor mice. In addition, PNP–sirolimus enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo. Clinical application of PNP–sirolimus is a promising strategy for human cancer treatment.Keywords: sirolimus, polymeric nanoparticle, anticancer, radiotherapy |
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