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

SIMIONI, YAMILA ROXANA; USSEGLIO, NADINA; BUTASSI, ESTEFANÍA; ALTUBE, MARIA JULIA; HIGA, LETICIA HERMINIA; ROMERO, EDER LILIA; SCHILRREFF, PRISCILA; MORILLA, MARIA JOSE

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY

EDITIONS SANTE

Año: 2025 vol. 105

1773-2247

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 reducethe use of topical corticosteroids, we have developed macrophage-targeted nanostructured archaeolipid carriersmade of a compritol, C50 dipolar carotenoid bacterioruberin (BR) and vitamin D3 (VD3) core, covered by sn 2,3ether 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, thiswork determined the effect of NAC-VD3 on a co-culture of THP-1 macrophages and 3T3 fibroblast irritated withlipopolysaccharide (LPS). The wound healing capacity, antifungal activity against Candida albicans, andbiocompatibility in normal human epidermal keratinocytes (NHEK) and dermal fibroblasts (NHDF) of NAC-VD3,were also assessed. NAC-VD3 (70 ± 14 nm; 0.45 ± 0.01 polydispersity index, − 31.7 ± 0.6 ζ potential; 3.4 ±0.24 mg/mL VD3 and 352 ± 126 μg/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 werereduced to same extent, while TNF-α levels were reduced to a greater degree than with 10 μg/mL of the corticosteroid dexamethasone. NAC-VD3 was non-cytotoxic on NHDF and NHEK cells, showing also wound-healingpotential. 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 agentwith wound healing and antimicrobial activities that deserves future in vivo exploration