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Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.
Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.
Low thermal conductivity boulder with high porosity identified on C-type asteroid (162173) Ryugu
(2019)
C-type asteroids are among the most pristine objects in the Solar System, but little is known about their interior structure and surface properties. Telescopic thermal infrared observations have so far been interpreted in terms of a regolith-covered surface with low thermal conductivity and particle sizes in the centimetre range. This includes observations of C-type asteroid (162173) Ryugu1,2,3. However, on arrival of the Hayabusa2 spacecraft at Ryugu, a regolith cover of sand- to pebble-sized particles was found to be absent4,5 (R.J. et al., manuscript in preparation). Rather, the surface is largely covered by cobbles and boulders, seemingly incompatible with the remote-sensing infrared observations. Here we report on in situ thermal infrared observations of a boulder on the C-type asteroid Ryugu. We found that the boulder’s thermal inertia was much lower than anticipated based on laboratory measurements of meteorites, and that a surface covered by such low-conductivity boulders would be consistent with remote-sensing observations. Our results furthermore indicate high boulder porosities as well as a low tensile strength in the few hundred kilopascal range. The predicted low tensile strength confirms the suspected observational bias6 in our meteorite collections, as such asteroidal material would be too frail to survive atmospheric entry7
Low thermal conductivity boulder with high porosity identified on C-type asteroid (162173) Ryugu
(2019)
C-type asteroids are among the most pristine objects in the Solar System, but little is known about their interior structure and surface properties. Telescopic thermal infrared observations have so far been interpreted in terms of a regolith-covered surface with low thermal conductivity and particle sizes in the centimetre range. This includes observations of C-type asteroid (162173) Ryugu1,2,3. However, on arrival of the Hayabusa2 spacecraft at Ryugu, a regolith cover of sand- to pebble-sized particles was found to be absent4,5 (R.J. et al., manuscript in preparation). Rather, the surface is largely covered by cobbles and boulders, seemingly incompatible with the remote-sensing infrared observations. Here we report on in situ thermal infrared observations of a boulder on the C-type asteroid Ryugu. We found that the boulder’s thermal inertia was much lower than anticipated based on laboratory measurements of meteorites, and that a surface covered by such low-conductivity boulders would be consistent with remote-sensing observations. Our results furthermore indicate high boulder porosities as well as a low tensile strength in the few hundred kilopascal range. The predicted low tensile strength confirms the suspected observational bias6 in our meteorite collections, as such asteroidal material would be too frail to survive atmospheric entry7.