A Pharmacokinetic Model for Quantifying the Effect of Vascular Permeability on the Choice of Drug Carrier: A Framework for Personalized Nanomedicine

作者：Kirtane Ameya R; Siegel Ronald A^*; Panyam Jayanth

来源：Journal of Pharmaceutical Sciences, 2015, 104(3): 1174-1186.

DOI：10.1002/jps.24302

• chemotherapy
• vascular pore size
• vascular pore fraction
• particle size
• controlled release
• delivery
• enhanced permeability and retention (EPR) effect
• anticancer drug delivery
• nanoparticles
• cancer
• pharmacokinetics
• pharmacodynamics

Drug carriers in the approximate to 100 nm size range are of considerable interest in the field of cancer therapy because of their ability to passively accumulate in tumors. Tailoring the physicochemical properties of these carriers to individual patient requirements will help exploit their full therapeutic potential. Here, we present a pharmacokinetic model to explain how vascular physiology could be used to guide the optimal choice of specific formulation parameters. We find that in order to maximize the benefit-to-risk ratio, nanosystems should be confined to a specific particle size range. The optimal particle size range is dictated by the vascular pore size of not only the tumor tissue but also of the normal organs. Additionally, the duration of drug release is a key variable that can be used to maximize the therapeutic benefit of nanomedicine. Our model further suggests that the enhanced permeability and retention effect is not necessarily a universal outcome for every nanocarrier in every tumor model but will only be observed for nanoparticles of a specific size range. This optimal size range, in turn, is governed by the vascular physiology of the tumor and of non-target organs.

• 出版日期2015-3