Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft

被引:121
作者
Chu, Kevin S. [1 ]
Hasan, Warefta [2 ]
Rawal, Sumit [1 ]
Walsh, Mark D. [1 ]
Enlow, Elizabeth M. [2 ]
Luft, J. Christopher [3 ]
Bridges, Arlene S. [4 ]
Kuijer, Jennifer L. [1 ]
Napier, Mary E. [2 ,3 ,5 ]
Zamboni, William C. [1 ,3 ,6 ,7 ,8 ]
DeSimone, Joseph M. [1 ,2 ,3 ,7 ,8 ,9 ,10 ,11 ,12 ]
机构
[1] Univ N Carolina, Dept Pharmaceut Sci, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[4] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA
[5] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
[6] Univ N Carolina, Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC 27599 USA
[7] Univ N Carolina, Carolina Ctr Canc Nanotechnol Excellence, Chapel Hill, NC 27599 USA
[8] Univ N Carolina, Eshelman Sch Pharm, Dept Pharmacol, Chapel Hill, NC 27599 USA
[9] Univ N Carolina, Inst Nanomed, Chapel Hill, NC 27599 USA
[10] Univ N Carolina, Inst Adv Mat, Chapel Hill, NC 27599 USA
[11] N Carolina State Univ, Dept Chem & Biomol Engn, Raleigh, NC 27695 USA
[12] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst Canc Res, New York, NY 10021 USA
关键词
Soft-lithography; PLGA; Nanoparticle; Shape; Pharmacokinetics; PHASE-III TRIAL; MACROMOLECULAR THERAPEUTICS; FORMULATION; PACLITAXEL; INTERNALIZATION; DOXORUBICIN; PARTICLES; DESIGN; AGENT; TIME;
D O I
10.1016/j.nano.2012.11.008
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
The particle fabrication technique PRINT (R) was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80 nm; height=320 nm (PRINT-Doc-80x320) and d=200 nm; h=200 nm (PRINT-Doc-200x200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was similar to 20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was similar to 18-fold (PRINT-Doc-80x320) and similar to 33-fold (PRINT-Doc-200x200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently led to increased tumor exposure of Docetaxel from 0 to 168 h (similar to 53% higher for PRINT-Doc-80x320 and similar to 76% higher for PRINT-Doc-200x200 particles). PRINT-Doc-80x320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200x200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system. From the Clinical Editor: In this study, the plasma, tumor, and tissue pharmacokinetics of different Docetaxel nanoparticles of precise shape and size were characterized in mice with human ovarian carcinoma xenograft. It is concluded that the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:686 / 693
页数:8
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