Topical co-delivery of vitamin D3 (VD3) and bacterioruberin for psoriasis treatment: formulation and in vitro studies

Y SIMIONI; P SCHILRREFF; EL ROMERO; MJ MORILLA

Mar del Plata

Congreso; SAIC.SAFE.SAB.SAP 2019; 2019

Psoriasis, a chronic immune-mediated disease, is characterized by excessive growth and abnormal differentiation of keratinocytes, angiogenesis, infiltration of neutrophils and inflammatory cells and cytokine production. Calcipotriol (vitamin D3 analogue) inhibits dendritic cells and IL-2 and IL-6 production by epidermal T cells, suppressing epidermal proliferation and differentiation. On the other hand, bacterioruberin (BR), the major C50 carotenoid found in halophilic Archaea, is one of the highest efficient natural antioxidants. However, the high hydrophobicity of VD3 and BR, and their susceptibility to chemical degradation impair its topical administration. The objective of this work was to combine the high antioxidant activity of BR with VD3 in one nanoparticle (VD3-BR-NP) to be administered by the topical route. The BR extract (350 µg BR/g dry Halorubrum tebenquichense culture) showed the typical three-fingered profile (460, 490 and 525 nm) spectrum and an inhibitory concentration providing 50 % reduction of the DPPH radical (IC50) of 21 µg/ml. NP made of a core of compritol and BR extract (50, 75 and 100 % of BR) covered by a shell of polar archaeolipids from H. tebenquichense and Tween 80 (2; 2; 1.2; 3% w/w) were prepared by homogenization-ultrasonication. The best formulation (50 % BR) in terms of smaller size (67 nm), high colloidal stability (6 months), lower cytotoxicity (5 % at 0.02 mg/ml LN) and high uptake by macrophages and keratinocytes was loaded with VD3. Nanosized (75 ± 2 nm), monodisperse(polydispersity index 0.496 ± 0.053), negative potential (-36 ± 0.3 mV), 6.5 mg/ml VD3 and IC50 to 4,8 µg/ml (activity was potentiated by co-encapsulation) VD3-BR-NP were obtained. Effectiveness of VD3-BR-NP was assessed on an in vitro psoriatic model and compared with conventional NP (lacking BR). VD3-BR-NP, and no conventional NP, showed anti-inflammatory and antioxidant activity. Concluding, VD3-BR-NP deserves further studies as promising topical option for treatment of psoriasis.