Enhancing the anti-psoriatic activity of vitamin D3 employing nanostructured archaeolipid carriers

Abstract

Psoriasis (Ps) is a multifactorial autoimmune skin disease, where oxidative stress plays a key role in promoting a vicious producing cycle between keratinocytes and immune cells. Vitamin D3 (VD3) regulates the differentiation, apoptosis, and proliferation of keratinocytes, also displaying antioxidant and anti-inflammatory activities. Previous attempts of using topical VD3 as anti-psoriatic agent, failed because of its poor solubility, high hydrophobicity, structural lability, and low bioavailability. Specifically tailored nanoparticles for topical co-delivery of VD3 and antioxidants to activated keratinocytes and macrophages could make Ps treatments more efficient. In this work, structural features, and in vitro activity of nanostructured archaeolipid carriers (NAC) containing VD3 plus the antioxidant C50 dipolar carotenoid bacterioruberin (BR) (NAC-VD3), are presented. Ultra-small (70 nm), −39 mV ζ potential, ∼5 mg VD3/ml, 0.35 BR μg/ml NAC-VD3, with good storage stability (at least 6 month) consisted of a compritol and BR core, covered by a shell of sn 2,3 ether linked archaeolipids and Tween 80 (2: 2: 1.2: 3% w/w) were obtained. Raman, DSC and SAXS analysis showed that VD3 was trapped within the disordered compritol-BR core, impairing its fast release, and protecting VD3 against thermal degradation. NAC-VD3 were extensively captured and displayed high anti-proliferative (65%), anti-inflammatory (IL-8 release) and antioxidant activities (ROS reduction) on a psoriatic model made of CaCl2 differentiated-imiquimod stimulated HaCaT cells, and on lipopolysaccharide induced THP-1 macrophages. Interestingly, the BR extract alone displayed high anti-Staphylococcus aureus activity including anti-biofilm formation. Overall, the results suggest that NAC-VD3 protect the labile structure of VD3, while enhancing its anti-psoriatic activity and deserves further in vivo exploration.