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.
Highlights
With regard to personalized and innovative medicine, therapy strategies do focus on a special drug
In the past few decades, biomedical research has focused more and more on drug delivery research, which has become an established field in pharmaceutical science exploring multiple approaches.[1,2]. Besides their primary function to carry and release active agents, cellular interaction and uptake of the Drug delivery systems (DDS) depend on several DDS-specific parameters: as an example, material, size, stiffness, shape, surface charge and surface modification play an important role in this matter
Due to the fact that the Flow Cytometry (FCM) measurement, in general, allows no precise distinction between internalized microcarriers and microcarriers just adhering to the cell membrane, cells were treated in a specific manner: To remove adhering microcarriers in those experiments, all cell types were more intensively washed with enzyme compared to standard cell detaching procedure
Summary
With regard to personalized and innovative medicine, therapy strategies do focus on a special drug. In the past few decades, biomedical research has focused more and more on drug delivery research, which has become an established field in pharmaceutical science exploring multiple approaches.[1,2] besides their primary function to carry and release active agents, cellular interaction and uptake of the DDS depend on several DDS-specific parameters: as an example, material, size, stiffness, shape, surface charge and surface modification play an important role in this matter. 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.
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