TY  - JOUR
A1  - Edlich, Alexander
A1  - Gerecke, Christian
A1  - Giulbudagian, Michael
A1  - Neumann, Falko
A1  - Hedtrich, Sarah
A1  - Schaefer-Korting, Monika
A1  - Ma, Nan
A1  - Calderon, Marcelo
A1  - Kleuser, Burkhard
T1  - Specific uptake mechanisms of well-tolerated thermoresponsive polyglycerol-based nanogels in antigen-presenting cells of the skin
JF  - European Journal of Pharmaceutics and Biopharmaceutics
N2  - Engineered nanogels are of high value for a targeted and controlled transport of compounds due to the ability to change their chemical properties by external stimuli. As it has been indicated that nanogels possess a high ability to penetrate the stratum corneum, it cannot be excluded that nanogels interact with dermal dendritic cells, especially in diseased skin. In this study the potential crosstalk of the thermore-sponsive nanogels (tNGs) with the dendritic cells of the skin was investigated with the aim to determine the immunotoxicological properties of the nanogels. The investigated tNGs were made of dendritic polyglycerol (dPG) and poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)), as polymer conferring thermoresponsive properties. Although the tNGs were taken up, they displayed neither cytotoxic and genotoxic effects nor any induction of reactive oxygen species in the tested cells. Interestingly, specific uptake mechanisms of the tNGs by the dendritic cells were depending on the nanogels cloud point temperature (Tcp), which determines the phase transition of the nanoparticle. The study points to caveolae-mediated endocytosis as being the major tNGs uptake mechanism at 37 degrees C, which is above the Tcp of the tNGs. Remarkably, an additional uptake mechanism, beside caveolae-mediated endocytosis, was observed at 29 degrees C, which is the Tcp of the tNGs. At this temperature, which is characterized by two different states of the tNGs, macropinocytosis was involved as well. In summary, our study highlights the impact of thermoresponsivity on the cellular uptake mechanisms which has to be taken into account if the tNGs are used as a drug delivery system.
KW  - Dendritic cells
KW  - Drug delivery systems
KW  - Nanogel
KW  - Nanoparticle
KW  - Nanoparticle uptake
KW  - Nanotoxicology
Y1  - 2017
U6  - https://doi.org/10.1016/j.ejpb.2016.12.016
SN  - 0939-6411
SN  - 1873-3441
VL  - 116
SP  - 155
EP  - 163
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Zhang, Nan
A1  - Said, Andre
A1  - Wischke, Christian
A1  - Kral, Vivian
A1  - Brodwolf, Robert
A1  - Volz, Pierre
A1  - Boreham, Alexander
A1  - Gerecke, Christian
A1  - Li, Wenzhong
A1  - Neffe, Axel T.
A1  - Kleuser, Burkhard
A1  - Alexiev, Ulrike
A1  - Lendlein, Andreas
A1  - Schäfer-Korting, Monika
T1  - Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles - Composition-dependent skin penetration enhancement of a dye probe and biocompatibility
JF  - European Journal of Pharmaceutics and Biopharmaceutics
N2  - Nanoparticles can improve topical drug delivery: size, surface properties and flexibility of polymer nanoparticles are defining its interaction with the skin. Only few studies have explored skin penetration for one series of structurally related polymer particles with systematic alteration of material composition. Here, a series of rigid poly[acrylonitrile-co-(N-vinyl pyrrolidone)] model nanoparticles stably loaded with Nile Red or Rhodamin B, respectively, was comprehensively studied for biocompatibility and functionality. Surface properties were altered by varying the molar content of hydrophilic NVP from 0 to 24.1% and particle size ranged from 35 to 244 nm. Whereas irritancy and genotoxicity were not revealed, lipophilic and hydrophilic nanoparticles taken up by keratinocytes affected cell viability. Skin absorption of the particles into viable skin ex vivo was studied using Nile Red as fluorescent probe. Whilst an intact stratum corneum efficiently prevented penetration, almost complete removal of the horny layer allowed nanoparticles of smaller size and hydrophilic particles to penetrate into viable epidermis and dermis. Hence, systematic variations of nanoparticle properties allows gaining insights into critical criteria for biocompatibility and functionality of novel nanocarriers for topical drug delivery and risks associated with environmental exposure.
KW  - Biocompatibility testing
KW  - Drug delivery systems
KW  - Nanoparticle
KW  - Poly[acrylonitrile-co-(N-vinyl pyrrolidone)]
KW  - Polymers
KW  - Skin absorption
Y1  - 2017
U6  - https://doi.org/10.1016/j.ejpb.2016.10.019
SN  - 0939-6411
SN  - 1873-3441
VL  - 116
SP  - 66
EP  - 75
PB  - Elsevier
CY  - Amsterdam
ER  -