Nutlin-3 Loaded Ethosomes and Transethosomes to Prevent UV-Associated Skin Damage

Autor: Elisabetta Esposito, Francesca Ferrara, Markus Drechsler, Olga Bortolini, Daniele Ragno, Sofia Toldo, Agnese Bondi, Alessandra Pecorelli, Rebecca Voltan, Paola Secchiero, Giorgio Zauli, Giuseppe Valacchi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Life, Vol 14, Iss 1, p 155 (2024)
Druh dokumentu: article
ISSN: 2075-1729
DOI: 10.3390/life14010155
Popis: The skin’s protective mechanisms, in some cases, are not able to counteract the destructive effects induced by UV radiations, resulting in dermatological diseases, as well as skin aging. Nutlin-3, a potent drug with antiproliferative activity in keratinocytes, can block UV-induced apoptosis by activation of p53. In the present investigation, ethosomes and transethosomes were designed as delivery systems for nutlin-3, with the aim to protect the skin against UV damage. Vesicle size distribution was evaluated by photon correlation spectroscopy and morphology was investigated by cryogenic transmission electron microscopy, while nutlin-3 entrapment capacity was evaluated by ultrafiltration and HPLC. The in vitro diffusion kinetic of nutlin-3 from ethosomes and transethosomes was studied by Franz cell. Moreover, the efficiency of ethosomes and transethosomes in delivering nutlin-3 and its protective role were evaluated in ex vivo skin explants exposed to UV radiations. The results indicate that ethosomes and transethosomes efficaciously entrapped nutlin-3 (0.3% w/w). The ethosome vesicles were spherical and oligolamellar, with a 224 nm mean diameter, while in transethosome the presence of polysorbate 80 resulted in unilamellar vesicles with a 146 nm mean diameter. The fastest nutlin-3 kinetic was detected in the case of transethosomes, with permeability coefficients 7.4-fold higher, with respect to ethosomes and diffusion values 250-fold higher, with respect to the drug in solution. Ex vivo data suggest a better efficacy of transethosomes to promote nutlin-3 delivery within the skin, with respect to ethosomes. Indeed, nutlin-3 loaded transethosomes could prevent UV effect on cutaneous metalloproteinase activation and cell proliferative response.
Databáze: Directory of Open Access Journals
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