N‐heterocyclic carbene catalyzed photoenolization/Diels–Alder reaction of acid fluorides

The combination of light activation and N‐heterocyclic carbene (NHC) organocatalysis has enabled the use of acid fluorides as substrates in a UVA‐light‐mediated photochemical transformation previously observed only with aromatic aldehydes and ketones. Stoichiometric studies and TD‐DFT calculations support a mechanism involving the photoactivation of an ortho‐toluoyl azolium intermediate, which exhibits “ketone‐like” photochemical reactivity under UVA irradiation. Using this photo‐NHC catalysis approach, a novel photoenolization/Diels–Alder (PEDA) process was developed that leads to diverse isochroman‐1‐one derivatives

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

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

Novel Adhesive Nanocarriers Based on Mussel-Inspired Polyglycerols for the Application onto Mucosal Tissues

A synthetic route for adhesive core-multishell (CMS) nanocarriers for application to the oral mucosa was established using mussel-inspired catechol moieties. The three CMS nanocarriers with 8%, 13%, and 20% catechol functionalization were evaluated for loading capacity using Nile red, showing an overall loading of 1 wt%. The ability of Nile red loaded and functionalized nanocarriers to bind to a moist mucosal surface was tested in two complementary adhesion assays under static and dynamic conditions using monolayers of differentiated gingival keratinocytes. Adhesion properties of functionalized nanocarriers were compared to the adhesion of the non-functionalized nanocarrier. In both assays, the CMS nanocarrier functionalized with 8% catechol exhibited the strongest adhesion compared to its catechol-free counterpart and the CMS nanocarriers functionalized with 13% and 20% catechol

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

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