Preclinical evaluation of injectable sirolimus formulated with polymeric nanoparticle for cancer therapy

被引：31
|
作者：
Woo, Ha Na
Chung, Hye Kyung [3 ]
Ju, Eun Jin
Jung, Joohee [4 ]
Kang, Hye-Won [5 ]
Lee, Sa-Won [5 ]
Seo, Min-Hyo [5 ]
Lee, Jin Seong [6 ,7 ]
Lee, Jung Shin [8 ]
Park, Heon Joo [9 ]
Song, Si Yeol [1 ]
Jeong, Seong-Yun [2 ]
Choi, Eun Kyung [1 ,3 ]
机构：
[1] Univ Ulsan, Asan Med Ctr, Dept Radiat Oncol, Coll Med, Seoul 138736, South Korea
[2] Univ Ulsan, Asan Med Ctr, Coll Med, Inst Innovat Canc Res, Seoul 138736, South Korea
[3] Asan Med Ctr, Ctr Dev & Commercializat Anticanc Therapeut, Seoul, South Korea
[4] Duksung Womens Univ, Coll Pharm, Seoul, South Korea
[5] Samyang Pharmaceut R&D, Dept Parenteral Delivery Program, Taejon, South Korea
[6] Asan Med Ctr, Dept Radiol, Seoul, South Korea
[7] Asan Med Ctr, Res Inst Radiol, Seoul, South Korea
[8] Asan Med Ctr, Dept Internal Med, Seoul, South Korea
[9] Inha Univ, Coll Med, Dept Microbiol, Inchon, South Korea
来源：
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2012年 / 7卷
基金：
新加坡国家研究基金会;
关键词：
sirolimus; polymeric nanoparticle; anticancer; radiotherapy; MAMMALIAN TARGET; RAPAMYCIN; MTOR; PATHWAY; INHIBITION; NANOTECHNOLOGY;
D O I：
10.2147/IJN.S29480
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
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.
引用
收藏
页码：2197 / 2208
页数：12
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