Biocompatibility, anti-inflammatory, wound healing, and antifungal activity of macrophage targeted-bacterioruberin-vitamin D3 loaded nanoparticles

Inflammatory skin diseases such as psoriasis and atopic dermatitis which affect around 25 % of the adult population, are routinely treated with corticosteroids that produce a variety of adverse effects. In an effort to reduce the use of topical corticosteroids, we have developed macrophage-targeted nanostructured archaeolipid carriers made of a compritol, C50 dipolar carotenoid bacterioruberin (BR) and vitamin D3 (VD3) core, covered by sn 2,3 ether linked polar archaeolipids extracted from the halophilic archaea Halorubrum tebenquichense and Tween 80 (NAC-VD3). Given the relevant interplay between fibroblasts and macrophages in dermal inflammation, this work determined the effect of NAC-VD3 on a co-culture of THP-1 macrophages and 3T3 fibroblast irritated with lipopolysaccharide (LPS). The wound healing capacity, antifungal activity against Candida albicans, and biocompatibility in normal human epidermal keratinocytes (NHEK) and dermal fibroblasts (NHDF) of NAC-VD3, were also assessed. NAC-VD3 (70 f 14 nm; 0.45 f 0.01 polydispersity index,-31.7 f 0.6 zeta potential; 3.4 f 0.24 mg/mL VD3 and 352 f 126 mu g/mL BR) was extensively captured by both THP-1 macrophages and fibroblasts, displaying significant anti-inflammatory activity on the co-culture: the release of IL-6 and IL-8 were reduced to same extent, while TNF-alpha levels were reduced to a greater degree than with 10 mu g/mL of the corticosteroid dexamethasone. NAC-VD3 was non-cytotoxic on NHDF and NHEK cells, showing also wound-healing potential. Finally, while NAC-VD3 lacked antifungal activity, its core component BR alone, displayed antiCandida albicans activity. Overall, our results position NAC-VD3 as a promising topical anti-inflammatory agent with wound healing and antimicrobial activities that deserves future in vivo exploration.