Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy

被引：102

作者：

Chu, Kevin S. ^{[1
]}

Schorzman, Allison N. ^{[1
]}

Finniss, Mathew C. ^{[3
]}

Bowerman, Charles J. ^{[2
,3
]}

Peng, Lei ^{[1
]}

Luft, James C. ^{[2
,3
]}

Madden, Andrew J. ^{[1
]}

Wang, Andrew Z. ^{[3
,4
,6
,8
]}

Zamboni, William C. ^{[1
,3
,5
,6
,7
]}

DeSimone, Joseph M. ^{[1
,2
,3
,5
,6
,7
,8
,9
,10
,11
]}

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 Radiat Oncol, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Inst Pharmacogen & Individualized Therapy, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Carolina Ctr Canc Nanotechnol Excellence, Chapel Hill, NC 27599 USA

[7] Univ N Carolina, Dept Pharmacol, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[8] Univ N Carolina, Inst Nanomed, Chapel Hill, NC 27599 USA

[9] Univ N Carolina, Inst Adv Mat, Chapel Hill, NC 27599 USA

[10] N Carolina State Univ, Dept Chem & Biomol Engn, Raleigh, NC 27695 USA

[11] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst Canc Res, New York, NY 10021 USA

来源：

BIOMATERIALS | 2013年 / 34卷 / 33期

关键词：

Soft-lithography; Docetaxel; Polylactic acid; Drug loading; Pharmacokinetics; RETICULOENDOTHELIAL BLOCKADE; PACLITAXEL; LIPOSOMES; CHOLESTEROL; FORMULATION; TUMOR; DOXORUBICIN; PLGA;

D O I：

10.1016/j.biomaterials.2013.07.038

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Nanoparticle (NP) drug loading is one of the key defining characteristics of an NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRIN (R)), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：8424 / 8429

页数：6

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