title: A pharmacokinetic model for quantifying the effect of vascular permeability on the choice of drug carrier: a framework for personalized nanomedicine.
abstract: Drug carriers in the ∼ 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.
authors.affiliation: Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, 55455.
authors.forename: Ameya R
authors.initials: AR
authors.lastname: Kirtane
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Siegel
authors.forename: Jayanth
authors.initials: J
authors.lastname: Panyam
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002199:Capillary Permeability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006801:Humans; D008954:Models, Biological; D053758:Nanoparticles; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D016062:Porosity; D057285:Precision Medicine; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers
keywords: anticancer drug delivery; cancer; chemotherapy; controlled release/delivery; enhanced permeability and retention (EPR) effect; nanoparticles; particle size; pharmacokinetics/pharmacodynamics; vascular pore fraction; vascular pore size