Efficacy of topically applied rapamycin-loaded redox-sensitive nanocarriers in a human skin/T cell co-culture model.

Rapamycin, also known as Sirolimus, is a promising anti-proliferative drug, but its therapeutic use for the topical treatment of inflammatory, hyperproliferative skin disorders is limited by insufficient penetration rates due to its high molecular weight (MW of 914.172 g/mol) and high lipophilicity. We have shown that core multi-shell (CMS) nanocarriers sensitive to oxidative environment can improve drug delivery to the skin.

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.

Topical Delivery of Rapamycin by Means of Microenvironment-Sensitive Core-Multi-Shell Nanocarriers: Assessment of Anti-Inflammatory Activity in an ex vivo Skin/T Cell Co-Culture Model.

Introduction: Rapamycin (Rapa) is an immunosuppressive macrolide that inhibits the mechanistic target of rapamycin (mTOR) activity. Thanks to its anti-proliferative effects towards different cell types, including keratinocytes and T cells, Rapa shows promise in the treatment of skin diseases characterized by cell hyperproliferation. However, Rapa skin penetration is limited due to its lipophilic nature (log = 4.

Oxidation-Sensitive Core-Multishell Nanocarriers for the Controlled Delivery of Hydrophobic Drugs.

A synthetic route for oxidation-sensitive core-multishell (osCMS) nanocarriers was established, and their drug loading and release properties were analyzed based on their structural variations. The nanocarriers showed a drug loading of 0.3-3 wt % for the anti-inflammatory drugs rapamycin and dexamethasone and the photosensitizer -tetra-hydroxyphenyl-porphyrin (THPP).