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

Limón, David; Talló Domínguez, Kirian; Garduño-Ramírez, María Luisa; Andrade, Berenice; Calpena, Ana C.; Pérez-García, Lluïsa

Authors

David Limón

Kirian Talló Domínguez

María Luisa Garduño-Ramírez

Berenice Andrade

Ana C. Calpena

Lluïsa Pérez-García



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 1:1 gelator:drug 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.

Journal Article Type Article
Publication Date 2019-09
Journal Colloids and Surfaces B: Biointerfaces
Print ISSN 0927-7765
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 181
Pages 657-670
APA6 Citation Limón, D., Talló Domínguez, K., Garduño-Ramírez, M. L., Andrade, B., Calpena, A. C., & Pérez-García, L. (2019). Nanostructured supramolecular hydrogels: Towards the topical treatment of Psoriasis and other skin diseases. Colloids and Surfaces B: Biointerfaces, 181, 657-670. doi:10.1016/j.colsurfb.2019.06.018
DOI https://doi.org/10.1016/j.colsurfb.2019.06.018
Keywords Nanopharmacotherapy; Hydrogel; Psoriasis; Drug delivery; Supramolecular chemistry; Skin permeation; In vivo studies
Publisher URL https://www.sciencedirect.com/science/article/pii/S0927776519304229?via%3Dihub
Additional Information This article is maintained by: Elsevier; Article Title: Nanostructured supramolecular hydrogels: Towards the topical treatment of Psoriasis and other skin diseases; Journal Title: Colloids and Surfaces B: Biointerfaces; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.colsurfb.2019.06.018; Content Type: article; Copyright: © 2019 Elsevier B.V. All rights reserved.
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