Redox-Responsive Nanocarrier for Controlled Release of Drugs in Inflammatory Skin Diseases
Keerthana Rajes,
Karolina A. Walker,
Sabrina Hadam,
Fatemeh Zabihi,
Fiorenza Rancan,
Annika Vogt,
Rainer Haag
Affiliations
Keerthana Rajes
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Karolina A. Walker
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Sabrina Hadam
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Fatemeh Zabihi
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Fiorenza Rancan
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Annika Vogt
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Rainer Haag
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
A synthetic route for redox-sensitive and non-sensitive core multi-shell (CMS) carriers with sizes below 20 nm and narrow molecular weight distributions was established. Cyclic voltammetric measurements were conducted characterizing the redox potentials of reduction-sensitive CMS while showcasing its reducibility through glutathione and tris(2-carboxyethyl)-phosphine as a proof of concept. Measurements of reduction-initiated release of the model dye Nile red by time-dependent fluorescence spectroscopy showed a pronounced release for the redox-sensitive CMS nanocarrier (up to 90% within 24 h) while the non-sensitive nanocarriers showed no release in PBS. Penetration experiments using ex vivo human skin showed that the redox-sensitive CMS nanocarrier could deliver higher percentages of the loaded macrocyclic dye meso-tetra (m-hydroxyphenyl) porphyrin (mTHPP) to the skin as compared to the non-sensitive CMS nanocarrier. Encapsulation experiments showed that these CMS nanocarriers can encapsulate dyes or drugs with different molecular weights and hydrophobicity. A drug content of 1 to 6 wt% was achieved for the anti-inflammatory drugs dexamethasone and rapamycin as well as fluorescent dyes such as Nile red and porphyrins. These results show that redox-initiated drug release is a promising strategy to improve the topical drug delivery of macrolide drugs.
