3-D Tissue Culture Systems for the Evaluation and Optimization of Nanoparticle-Based Drug Carriers

Abstract

Nanoparticle carriers are attractive vehicles for a variety of drug delivery applications. In order to evaluate nanoparticle formulations for biological efficacy, monolayer cell cultures are typically used as in vitro testing platforms. However, these studies sometimes poorly predict the efficacy of the drug in vivo. The poor in vitro and in vivo correlation may be attributed in part to the inability of twodimensional cultures to reproduce extracellular barriers, and may also be due to differences in cell phenotype between cells cultured as monolayers compared to cells in native tissue. In order to more accurately predict in vivo results it is desirable to test nanoparticle therapeutics in cells cultured in three-dimensional models that mimic in vivo conditions. In this review we discuss some 3-D culture systems that have been used to assess nanoparticle delivery and highlight several implications for nanoparticle design garnered from studies using these systems. While our focus will be on nanoparticle drug formulations, many of the systems discussed here could, or have been, used for the assessment of small molecule or peptide/protein drugs. We also offer some examples of advancements in 3-D culture that could provide even more highly predictive data for designing nanoparticle therapeutics for in vivo applications.

Thermoresponsive Polymers for Biomedical Applications

“…To name a few, these obstacles include the drugs': low solubility, environmental or enzymatic degradation, fast clearance rates from the body, non-specific toxicity and inability to cross the biological barriers [32,33]. In order to overcome these obstacles, drug delivery carriers are being used, most of which are based on polymers [32][33][34]. Released drug concentration over time.…”

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

“…Not only cellular organisation and polarisation are lost in classical 2D monocultures, cells also fail to produce an in vivo-like extracellular matrix (ECM). Cells are still able to produce and secrete ECM proteins in a 2D environment but the extent of ECM production is altered and the barrier formed is less dense and incomplete in comparison to the in vivo ECM 207 . This ECM is a very important factor as it is a natural barrier with small pores and therefore limits NP diffusion into a tissue 208 .…”

“…It was, for example, shown by Kuo et al that the epithelialmesenchymal-transition, which is a hallmark in the metastatic process, is promoted for several cancer cell lines when they are cultured as spheres 210 . Thus, it can be concluded that the cultivation conditions have a major influence on the cellular phenotype and function and that cellular responses following NP exposure are therefore likely to be drastically altered in a 3D model when compared to a conventional monolayer 207 .…”

An x-ray fluorescence imaging system for gold nanoparticle detection

“…Author: Please check whether the author names and journal title are okay as amended in reference 'Goodman et al (2009)…”