title: Correlation between the chemical composition of thermoresponsive nanogels and their interaction with the skin barrier.
abstract: In this paper we present a comprehensive study for the ability of thermoresponsive nanogels (tNG) to act as cutaneous penetration enhancers. Given the unique properties of such molecular architectures with regard to their chemical composition and thermoresponsive properties, we propose a particular mode of penetration enhancement mechanism, i.e. hydration of the stratum corneum. Different tNG were fabricated using dendritic polyglycerol as a multifunctional crosslinker and three different kinds of thermoresponsive polymers as linear counterpart: poly(N-isopropylacrylamide) (pNIPAM), p(di(ethylene glycol) methyl ether methacrylate - co - oligo ethylene glycol methacrylate) (DEGMA-co-OEGMA475), and poly(glycidyl methyl ether - co - ethyl glycidyl ether) (tPG). Excised human skin was investigated by means of fluorescence microscopy, which enabled the detection of significant increment in the penetration of tNG as well as the encapsulated fluorescein. The morphology of the treated skin samples was thoroughly investigated by transmission electron microscopy and stimulated Raman spectromicroscopy. We found that tNG can perturbate the organization of both proteins and lipids in the skin barrier, which was attributed to tNG hydration effects. Interestingly, different drug delivery properties were detected and the ability of each investigated tNG to enhance skin penetration correlated well with the degree of induced stratum corneum hydration. The differences in the penetration enhancements could be attributed to the chemical structures of the nanogels used in this study. The most effective stratum corneum hydration was detected for nanogels having additional or more exposed polyether structure in their chemical composition.
authors: Freie Universität Berlin, Institute for Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany.
authors: Michael
authors: M
authors: Giulbudagian
authors: Clinical Research Center of Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: fiorenza.rancan@charite.de.
authors: Fiorenza
authors: F
authors: Rancan
authors: Freie Universität Berlin, Institute for Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany.
authors: André
authors: A
authors: Klossek
authors: Freie Universität Berlin, Institute for Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany.
authors: Kenji
authors: K
authors: Yamamoto
authors: Clinical Research Center of Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Jana
authors: J
authors: Jurisch
authors: Clinical Research Center of Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Victor Colombo
authors: VC
authors: Neto
authors: Institute for Anatomy, Charité-Universitatsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Petra
authors: P
authors: Schrade
authors: Institute for Anatomy, Charité-Universitatsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Sebastian
authors: S
authors: Bachmann
authors: Freie Universität Berlin, Institute for Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany. Electronic address: ruehl@zedat.fu-berlin.de.
authors: Eckart
authors: E
authors: Rühl
authors: Clinical Research Center of Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Ulrike
authors: U
authors: Blume-Peytavi
authors: Clinical Research Center of Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Annika
authors: A
authors: Vogt
authors: Freie Universität Berlin, Institute for Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany. Electronic address: marcelo.calderon@fu-berlin.de.
authors: Marcelo
authors: M
authors: Calderón
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D019793:Fluorescein / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008055:Lipids / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013696:Temperature
chemical_list: D004337:Drug Carriers; D008055:Lipids; D011108:Polymers; D011506:Proteins; D019793:Fluorescein
keywords: Drug delivery; Nanogels; Skin barrier; Stimulated Raman spectromicroscopy; Stratum corneum; Thermoresponsive