Comparison of Quantum Dot Biodistribution with a Blood-Flow-Limited Physiologically Based Pharmacokinetic Model
ABSTRACT A physiologically based pharmacokinetic model with partition coefficients estimated from quantum dot (QD) 705 biodistribution was compared with the biodistribution of other QDs in mice and rats to determine the model's predictive ability across QD types, species, and exposure routes. The model predicted the experimentally observed persistence of QDs in tissues but not early time profiles or different QD biodistribution. Therefore, more complex models will be needed to better predict QD biodistribution in vivo.
SourceAvailable from: Zhoumeng Lin[Show abstract] [Hide abstract]
ABSTRACT: Metallic nanoparticles (NPs) have been widely applied in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. This review focuses on gold and silver (Ag) NPs, and briefly discusses iron oxide, titanium dioxide (TiO2), and zinc oxide NPs. Pharmacokinetics of metallic NPs depends on the particle type, size, surface charge, surface coating, protein binding, exposure route, dose, and species. Generally, blood half-life is shorter in rodents than in larger laboratory animals (e.g., rabbits or monkeys) and differs between intravenous and oral exposures. Oral, dermal, or inhalational absorption is low (≤5%), but may increase with smaller sizes, negative charge, and appropriate coatings. Metallic NPs can be distributed throughout the body, primarily accumulating in the liver, spleen, and lymph node due to nonspecific uptake by reticuloendothelial cells, and could remain in the body for ≥6 months. Metallic NPs (≤100 nm) can cross the blood–brain barrier (BBB), favored by coating with BBB-permeable neuropeptides. Placental transfer depends on the stage of embryonic/placental maturation and surface composition, and may be enhanced by coating with biocompatible molecules (e.g., ferritin or polyethylene glycol). Renal and biliary excretion is generally low due to persistent accumulation in tissues, but renal elimination could be substantially increased with smaller sizes and specific coatings (e.g., glutathione). Physiologically based pharmacokinetic models for gold/dendrimer composite nanodevices, AgNPs, and TiO2NPs have been developed in rats and the AgNP and TiO2NP models have been extrapolated to humans to support risk assessment and nanomedicine applications.For further resources related to this article, please visit the WIREs website.Conflict of interest: The authors have declared no conflicts of interest for this article.Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 10/2014; 7(2). DOI:10.1002/wnan.1304 · 4.24 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Recently, nanoparticles (NPs) have been established as ideal drug delivery vehicles for treating cancer. This is due to the enhanced permeability and retention (EPR) effect that is a direct result of the angiogenic nature of the tumor tissue and its ability to sequester chemotherapeutics from healthy tissues. Ideal drug delivery nanocarriers will exploit the EPR effect, accumulate in the tumorous tissue, and be able to release the drugs at a high concentration where needed, thereby reducing undesirable side effects. In order to determine ideal NP qualities that enable drugs to be delivered in such a manner, extensive testing in biological systems is required. However, it is impractical to study new potential nanocarriers in humans or in mammalian models due to the potential adverse consequences, low throughput, and high cost. Simpler models would allow for higher throughput screening of nanocarrier vehicles. This review outlines the most recent advances in alternative model assays and their significance in testing NPs en route to the clinic. In decreasing complexity, we examine zebrafish embryos, the chorioallantoic membrane of the chicken embryo, multicell static and flow-based assays, and single cell assays for efficacy, accuracy and utility as predictors for human therapeutic outcomes.Journal of Biomedical Nanotechnology 09/2015; 10(9). DOI:10.1166/jbn.2014.1931 · 7.58 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Nanotechnology offers a new platform for therapeutic delivery of antiretrovirals to the central nervous system (CNS). Nanoformulated antiretroviral drugs offer multifunctionality, that is, the ability to package multiple diagnostic and therapeutic agents in the same nanocompose, along with the added provisions of site-directed delivery, delivery across the blood-brain-barrier (BBB), and controlled release of therapeutics. We studied the viability of dendrimers and dendriplexes in human primary astrocytes, as well as their uptake by these astrocytes. Functional validation was performed by using specific siRNA against HIV-1 Nef to interfere to HIV-1 infectivity. A high efficiency in Nef silencing, reducing HIV-1 infectivity was observed in astrocytes treated with dendriplexes compared with control or siRandom treated astrocytes. More interestingly, we studied the biodistribution of the second generation of carbosilane dendrimer loaded with FITC (2G-(SNMe3I)11-FITC) in vivo, in BALB/c mice. Dendriplexes were inoculated into BALB/c mice by the retro-orbital venous plexus, and their localization was determined after 1 and 24h post-injection. Dendriplexes were detected inside the brain by a sensitive imaging system of fluorescent imaging in vivo (IVIS Lumina), and by confocal microscopy analysis of sections of OCT-embedded tissues. The 2G-(SNMe3I)11-FITC dendrimer transported efficiently siRNA into the brain, crossing the BBB. Moreover, this dendrimer successfully delivered and transfected siRNA to HIV-infected human primary astrocytes and achieved gene silencing without causing cytotoxicity. These results highlight the potential of this nanoformulation in the treatment of neurological disorders. Copyright © 2014. Published by Elsevier B.V.Journal of Controlled Release 01/2015; 200. DOI:10.1016/j.jconrel.2014.12.042 · 7.26 Impact Factor