A novel liposomal formulation of FTY720 (Fingolimod) for promising enhanced targeted delivery

被引：31
作者：
Mao, Yicheng [1 ,2 ]
Wang, Jiang [2 ]
Zhao, Yuan [2 ]
Wu, Yun [1 ,3 ]
Kwak, Kwang Joo [1 ,3 ]
Chen, Ching-Shih [4 ]
Byrd, John C. [5 ]
Lee, Robert J. [1 ,2 ]
Phelps, Mitch A. [2 ]
Lee, L. James [1 ,3 ]
Muthusamy, Natarajan [5 ]
机构：
[1] Ohio State Univ, Ctr Affordable Nanoengn Polymer Biomed Devices CA, Columbus, OH 43210 USA
[2] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA
[3] Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA
[4] Ohio State Univ, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA
[5] Ohio State Univ, Dept Internal Med, Div Hematol & Oncol, Columbus, OH 43210 USA
来源：
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2014年 / 10卷 / 02期
关键词：
FTY720; Liposome; Leukemia; Drug delivery; CD37; Nanotechnology; CHRONIC LYMPHOCYTIC-LEUKEMIA; THERAPEUTIC-EFFICACY; PRECLINICAL ACTIVITY; TRANSPLANT PATIENTS; IMMUNOLIPOSOMES; APOPTOSIS; PHARMACOKINETICS; ACTIVATION; MECHANISM; DRUG;
D O I：
10.1016/j.nano.2013.08.001
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
We describe here the development and characterization of the physicochemical and pharmacokinetic properties of a novel liposomal formulation for FTY720 delivery, LP-FTY720. The mean diameter of LP-FTY720 was similar to 157 nm, and the FTY720 entrapment efficiency was similar to 85%. The liposomal formulation protected FTY720 from degradation in aqueous buffer and showed toxicity in CLL patient B cells comparable to that of free FTY720. Following intravenous injection in ICR mice, LP-FTY720 had an increased elimination phase half-life (similar to 28 vs. similar to 19 hr) and decreased clearance (235 vs. 778 mL/h/kg) compared to the free drug. Antibodies against CD19, CD20 and CD37 were incorporated into LP-FTY720, which provided targeted delivery to CLL patient B cells and thus achieved higher killing efficacy. The novel liposomal carrier of FTY720 demonstrated improved pharmacokinetic properties, comparable activity, and a potential platform for targeted delivery to CLL by overcoming the limited application of free FTY720 to B malignancy treatment. Published by Elsevier Inc.
引用
收藏
页码：393 / 400
页数：8
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