Redox-Responsive Nanocarrier for Controlled Release of Drugs in Inflammatory Skin Diseases

• Main Authors: Keerthana Rajes (Author), Karolina A. Walker (Author), Sabrina Hadam (Author), Fatemeh Zabihi (Author), Fiorenza Rancan (Author), Annika Vogt (Author), Rainer Haag (Author)
• Format: Book
• Published: MDPI AG, 2020-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics13010037; 1999-4923
• Keywords: CMS nanocarriers; disulfide; redox; stimuli responsive; cyclic voltammetry; skin penetration; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 13, Iss 1, p 37 (2020)

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 (<i>m</i>-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.