title: Effects of thermoresponsivity and softness on skin penetration and cellular uptake of polyglycerol-based nanogels.
abstract: Nanogels are water soluble cross-linked polymer networks with nanometer size dimensions that can be designed to incorporate different types of compounds and are promising carrier systems for drugs and biological molecules. In this study, the interactions of thermoresponsive nanogels (tNGs) with the human skin barrier and underlying epidermis cells were investigated with the aim of using such macromolecules to improve dermal and transdermal drug delivery. The investigated tNGs were made of acrylated dendritic polyglycerol, as water soluble cross-linker, and of oligo ethylene glycol methacrylate (OEGMA) as subunit conferring thermoresponsive properties. tNGs with different polymer transition temperatures were tagged with Rhodamine B (RhdB) and analyzed for their physicochemical properties. We found that tNGs with cloud point temperatures (Tcps) of 38 °C (tNG-RhdB-T38) lost softness (measured by PeakForce quantitative nanomechanics, QNM) and aggregated to bigger sized particles (measured as increase of particle average size by dynamic light scattering, DLS) when temperature changed from 15 to 37 °C. On the contrary, at the same conditions, tNGs with higher Tcps (tNG-RhdB-T55) did not show any significant changes of these characteristics. Applied on excised human skin, both tNGs penetrated deep in the stratum corneum (SC). Small amounts of tNGs were detected also in cells of the viable epidermis. Interestingly, whereas tNG softness correlated with higher penetration in SC, a better cellular uptake was observed for the thermoresponsive tNG-RhdB-T38. We conclude that soft nanocarriers possess a high SC penetration ability and that thermoresponsive nanogels are attractive carrier systems for the targeting of drugs to epidermis cells.
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: fiorenza.rancan@charite.de.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Rancan
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
authors.forename: Mazdak
authors.initials: M
authors.lastname: Asadian-Birjand
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Serap
authors.initials: S
authors.lastname: Dogan
authors.affiliation: Physikalische Chemie und Theoretische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Graf
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
authors.forename: Luis
authors.initials: L
authors.lastname: Cuellar
authors.affiliation: Institute of Vegetative Anatomy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Lommatzsch
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume-Peytavi
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany. Electronic address: marcelo.calderon@fu-berlin.de.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Calderón
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Vogt
mesh_terms: D000279:Administration, Cutaneous; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics*; D005782:Gels / Q000737:chemistry / Q000493:pharmacokinetics*; D005990:Glycerol / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D005782:Gels; D011108:Polymers; C043941:polyglycerol; D005990:Glycerol
keywords: Cellular uptake; Dermal delivery; Skin penetration; Thermoresponsive nanogel