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

ABSTRACT: PURPOSE: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. METHODS: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. RESULTS:Cisplatin-loaded PLGA NPs are most effective in decreasing t

SUBMITTER: Miller HA 

PROVIDER: S-EPMC7384478 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature