Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles

JOURNAL OF CONTROLLED RELEASE

卷:172

Review

Ernsting, Mark J.^1,2  Murakami, Mami¹  Roy, Aniruddha¹  Li, Shyh-Dar^1,3,4 

[1] Ontario Inst Canc Res, Drug Discovery Program, Toronto, ON M5G 0A3, Canada

[2] Ryerson Univ, Fac Architectural Sci & Engn, Toronto, ON M5B 1Z2, Canada

[3] Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada

[4] Univ Hlth Network, Techna Inst, Toronto, ON M5G 1P5, Canada

关键词: Nanoparticle;    Pharmacokinetics;    Biodistribution;    Tumor microenvironment;    Intratumoral penetration;   

DOI  :  10.1016/j.jconrel.2013.09.013

来源: Elsevier

【 摘 要 】

Nanoparticle drug delivery to the tumor is impacted by multiple factors: nanoparticles must evade clearance by renal filtration and the reticuloendothelial system, extravasate through the enlarged endothelial gaps in tumors, penetrate through dense stroma in the tumor microenvironment to reach the tumor cells, remain in the tumor tissue for a prolonged period of time, and finally release the active agent to induce pharmacological effect. The physicochemical properties of nanoparticles such as size, shape, surface charge, surface chemistry (PEGylation, ligand conjugation) and composition affect the pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. On the other hand, tumor biology (blood flow, perfusion, permeability, interstitial fluid pressure and stroma content) and patient characteristics (age, gender, tumor type, tumor location, body composition and prior treatments) also have impact on drug delivery by nanoparticles. It is now believed that both nanoparticles and the tumor microenvironment have to be optimized or adjusted for optimal delivery. This review provides a comprehensive summary of how these nanoparticle and biological factors impact nanoparticle delivery to tumors, with discussion on how the tumor microenvironment can be adjusted and how patients can be stratified by imaging methods to receive the maximal benefit of nanomedicine. Perspectives and future directions are also provided. (C) 2013 Elsevier B. V. All rights reserved.

【 授权许可】

Free