Pharmaceutical Research

, 36:185 | Cite as

Pharmacokinetic/Pharmacodynamics Modeling of Drug-Loaded PLGA Nanoparticles Targeting Heterogeneously Vascularized Tumor Tissue

  • Hunter A. Miller
  • Hermann B. FrieboesEmail author
Research Paper



Nanoparticle-mediated drug delivery and efficacy for cancer applications depends on systemic as well as local microenvironment characteristics. Here, a novel coupling of a nanoparticle (NP) kinetic model with a drug pharmacokinetic/pharmacodynamics model evaluates efficacy of cisplatin-loaded poly lactic-co-glycolic acid (PLGA) NPs in heterogeneously vascularized tumor tissue.


Tumor lesions are modeled with various levels of vascular heterogeneity, as would be encountered with different types of tumors. The magnitude of the extracellular to cytosolic NP transport is varied to assess tumor-dependent cellular uptake. NP aggregation is simulated to evaluate its effects on drug distribution and tumor response.


Cisplatin-loaded PLGA NPs are most effective in decreasing tumor size in the case of high vascular-induced heterogeneity, a high NP cytosolic transfer coefficient, and no NP aggregation. Depending on the level of tissue heterogeneity, NP cytosolic transfer and drug half-life, NP aggregation yielding only extracellular drug release could be more effective than unaggregated NPs uptaken by cells and releasing drug both extra- and intra-cellularly.


Model-based customization of PLGA NP and drug design parameters, including cellular uptake and aggregation, tailored to patient tumor tissue characteristics such as proportion of viable tissue and vascular heterogeneity, could help optimize the NP-mediated tumor drug response.


cancer nanotherapy cancer simulation mathematical modeling PLGA nanoparticles tumor heterogeneity 



Area-under the-curve


Extracellular matrix




Non-small cell lung cancer






Poly lactic-co-glycolic acid



HBF acknowledges partial support by the National Institutes of Health/National Cancer Institute Grant R15CA203605.

Supplementary material

11095_2019_2721_MOESM1_ESM.pdf (1.4 mb)
ESM 1 (PDF 1.35 mb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacology and ToxicologyUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of Bioengineering, Lutz Hall 419University of LouisvilleLouisvilleUSA
  3. 3.James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  4. 4.Center for Predictive MedicineUniversity of LouisvilleLouisvilleUSA

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