Activity of hydrogel-vitamin D3 /bacterioruberin nanoparticles on imiquimod-induced fibroblasts-keratinocytes spheroids

SIMIONI, YAMILA ROXANA; RICATTI, FEDERICO; SALVAY, ANDRÉS G.; JEREZ, HORACIO EMANUEL; SCHILRREFF, PRISCILA; ROMERO, EDER LILIA; MORILLA, MARIA JOSE

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY

EDITIONS SANTE

Año: 2024 vol. 97

1773-2247

Topical administration of vitamin D3 (VD3) analogs and corticosteroids is the mainstay treatment for mildlocalized psoriasis. VD3 however is an unstable class II drug (insoluble and permeable), classically formulated asunattractive viscous and oil-based ointments or creams. In this work, nanostructured archaeolipid carriers (NAC)with a core loaded with VD3 and the C50 dipolar carotenoid from halophilic archaea bacterioruberin (BR): NACVD3,were formulated into a carbopol hydrogel: gNAC-VD3. After its rheological characterization, its antiinflammatoryand antioxidant activity was assessed on bi-cellular spheroids, consisting of a core of fibroblastssurrounded by a ring of keratinocytes activated with imiquimod (IMQ) as a psoriasis model. gNAC-VD3 (0.8 mgVD3/135 μg BR/gram gel) conserved the antioxidant activity, showed pseudoplastic non-Newtonian behaviour,stability over time, good occlusion capacity and spreadability, all suitable properties for topical application inpatients with psoriasis. gNAC-VD3 did not decrease the viability of spheroids but significantly reduced therelease of proinflammatory cytokines (IL-8, IL-6, TNF-α), oxidative stress (ROS), and matrix metalloproteinasesfrom IMQ-induced spheroids to levels similar to the uninduced spheroids. Results suggest that gNAC-VD3 mayconstitute a potential anti-inflammatory agent for the topical treatment of mild psoriasis and deserves further invivo exploration.