Nanostructured supramolecular hydrogels: Towards the topical treatment of Psoriasis and other skin diseases.

ABSTRACT

Supramolecular hydrogels were synthesized using a bis-imidazolium based amphiphile, and incorporating chemically diverse drugs, such as the cytostatics gemcitabine hydrochloride and methotrexate sodium salt, the immunosuppressive drug tacrolimus, as well as the corticoid drugs betamethasone 17-valerate and triamcinolone acetonide, and their potential as drug delivery agents in the dermal treatment of Psoriasis was evaluated. The rheological behavior of gels was studied, showing in all cases suitable viscoelastic properties for topical drug delivery. Scanning electron microscopy (SEM) shows that the drugs included have a great influence on the gel morphology at the microscopic level, as the incorporation of gemcitabine hydrochloride leads to slightly thicker fibers, the incorporation of tacrolimus induces flocculation and spherical precipitates, and the incorporation of methotrexate forms curled fibers. 1H NMR spectroscopy experiments show that these drugs not only remain dissolved at the interstitial space, but up to 72% of either gemcitabine or methotrexate, and up to 38% of tacrolimus, is retained within the gel fibers in gels formed with a 11 gelatordrug molar ratio. This unique fiber incorporation not only protects the drug from degradation, but also importantly induces a Two Phase Exponential drug release, where the first phase corresponds to the drug dissolved in the interstitial space, while the second phase corresponds to the drug exiting from the gel fibers, and where the speed in each phase is in accordance with the physicochemical properties of the drugs, opening perspectives for controlled delivery. Skin permeation ex vivo tests show how these gels successfully promote the drug permeation and retention inside the skin for reaching their therapeutic target, while in vivo experiments demonstrate that they decrease the hyperplasia and reduce the macroscopic tissue damage typically observed in psoriatic skin, significantly more than the drugs in solution. All these characteristics, beside the spontaneous and easy preparation (room temperature and soft stirring), make these gels a good alternative to other routes of administration for Psoriasis treatment, increasing the drug concentration at the target tissue, and minimizing side effects.