Cellular interaction of a layer-by-layer based drug delivery system depending on material properties and cell types

Abstract

BackgroundDrug delivery systems (DDS) and their interaction with cells are a controversial topic in the development of therapeutic concepts and approaches. On one hand, DDS are very useful for protected and targeted transport of defined dosages of active agents. On the other hand, their physicochemical properties such as material, size, shape, charge, or stiffness have a huge impact on cellular uptake and intracellular processing. Additionally, even identical DDS can undergo a completely diverse interaction with different cell types. However, quite often in in vitro DDS/cell interaction experiments, those aspects are not considered and DDS and cells are randomly chosen.Methods and resultsHence, our investigations provide an insight into layer-by-layer designed microcarriers with modifications of only some of the most important parameters (surface charge, stiffness, and applied microcarrier/cell ratio) and their influence on cellular uptake and viability. We also considered the interaction of these differently equipped DDS with several cell types and investigated professional phagocytes (neutrophil granulocytes; macrophages) as well as non-professional phagocytes (epithelial cells) under comparable conditions. We found that even small modifications such as layer-by-layer (LbL)-microcarriers with positive or negative surface charge, or LbL-microcarriers with solid core or as hollow capsules but equipped with the same surface properties, show significant differences in interaction and viability, and several cell types react very differently to the offered DDS.ConclusionAs a consequence, the properties of the DDS have to be carefully chosen with respect to the addressed cell type with the aim to efficiently transport a desired agent.

The Metabolic Response of Various Cell Lines to Microtubule-Driven Uptake of Lipid- and Polymer-Coated Layer-by-Layer Microcarriers

“…Thereafter incubation with microcarriers was carried out for 16 h and at a micocarrier:cell ratio of 2:1. This time frame allowed for an optimal uptake and processing rate as revealed by our previous study, where uptake in different cell lines was shown to be completed at around 5–6 h [ 13 ]. While uptake for both, polymer and SLB microcarriers, progresses without loss of layer components, subsequent processing refers to passage of the endosomal-lysosomal compartment and the beginning of the disassembly of the lipid bilayer and polymer multilayer.…”

“…It is known, that cytoskeletal elements can naturally induce mechanical stress on the nucleus leading to nucleus confinement and deformation [ 36 ], an effect which is cell type dependent [ 37 ]. Additionally, mechanical deformation by externally added elements, such as functionalized microcarriers, seem not to lead to nucleus irritations, as no signs of apoptosis or necrosis could be found [ 13 ]. Thus, this system could then be adapted to transport active agents near the nucleus for specific applications, such as for nucleus-targeting cancer therapeutics [ 38 ].…”

“…Second, endocytotic processes are energy-dependent processes [ 11 ]. The release of these microcarriers from endosomes is characterised by a time-delay, which also depends on several parameters such as microcarrier size, material, charge, stiffness or respective functionalisation [ 12 , 13 , 14 ]. This in turn could reduce the availability of endosomes for cellular homeostasis and induce metabolic countermeasures in the target cell.…”

“…These cell types were selected based on various criteria. First, Vero, HEK293T/17 and A549 cells are already characterized in different microcarrier studies [ 10 , 11 , 13 , 24 ]. Second, they display a different metabolic background, e.g., the glycolytic tumour cell line A549 in comparison to HEK293T/17 with a high rate of aerobic respiration.…”

Ceria-Containing Hybrid Multilayered Microcapsules for Enhanced Cellular Internalisation with High Radioprotection Efficiency

“…It has previously been shown that microcapsules can be taken up by various cell types [ 45 ]. The uptake efficiency of microcapsules may depend on their size [ 46 ], charge of the outer layer [ 47 ], the type of polyelectrolytes used [ 48 ], the elasticity or deformability of the microcapsule shell [ 49 ] or their shape [ 50 ]. Here, human mesenchymal stem cells were used to analyse the endocytosis of nanoceria-loaded microcapsules using fluorescence microscopy ( Figure 3 a).…”