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      Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles.

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          Abstract

          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.

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          Author and article information

          Journal
          J Control Release
          Journal of controlled release : official journal of the Controlled Release Society
          Elsevier BV
          1873-4995
          0168-3659
          Dec 28 2013
          : 172
          : 3
          Affiliations
          [1 ] Drug Delivery and Formulation, Drug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario M5G 0A3, Canada; Ryerson University, Faculty of Architectural Science and Engineering, Toronto, Ontario M5B 1Z2, Canada.
          Article
          S0168-3659(13)00801-8 NIHMS540306
          10.1016/j.jconrel.2013.09.013
          3891171
          24075927
          d584b029-348a-4267-b39b-aa1388dba19f
          © 2013.
          History

          Biodistribution,Intratumoral penetration,Nanoparticle,Pharmacokinetics,Tumor microenvironment

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