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The properties of two hybrid nanoarchaeosomes (hybrid nanoARCs) made of archaeolipids extracted from the halophilic archaea Halorubrum tebenquichense and combining the properties of archaeolipid bilayers with metallic nanoparticles are explored here. BS-nanoARC, consisting of a nanoARC loaded with yerba mate ( Ilex paraguariensis) extract (YME)-biogenic silver nanoparticles (BSs), and [BS + BS-nanoARC], consistent of a BS-nanoARC core covered by an outer shell of BSs, were structurally characterized and their therapeutic activities screened. By employing 109 ± 5 µg gallic acid equivalents (GAEs) and 73.4 µg chlorogenic acid/ YME mg as a silver reductive agent, spherical, heterogeneously sized (~80 nm diameter), -27 mV ζ potential, 90% Ag 0 and λ max 420 nm BSs were obtained. We further prepared ~100-200 nm diameter, -57 mV ζ potential BS-nanoARC and ~300 nm diameter, -37 mV ζ potential [BS + BS-nanoARCs]. Freshly prepared and nebulized BS-nanoARCs reduced the release of TNF-α, IL-6 and IL-8 by LPS-irritated THP-1-macrophages and were highly anti-planktonic against S. aureus (MIC 90 : 13 ± 0.8 µg Ag/mL). While the nanoARCs and BS-nanoARCs were innocuous, freshly prepared [BS + BS-nanoARCs] magnified the cytotoxicity of BSs (IC 50 12 µg Ag/mL vs. IC 50 ~36 µg Ag/mL) on A549 cells. Such cytotoxicity remained after 30 days in the dark at 4 °C, while that of BSs was lost. Freshly prepared BSs also lost activity upon nebulization, whereas freshly prepared [BS + BS-nanoARCs] did not. However, the cytotoxicity of the [BS + BS-nanoARCs] was also lost when nebulized after 30 days of storage. Despite the harmful effects of storage and mechanical stress on the structure of the more active [BS + BS-nanoARCs], hybrid nanoARCs are promising examples of nanomedicines combining the properties of archaeolipids with antimicrobial silver nanoparticles and anti-inflammatory polyphenols that could complement oncologic therapies, reducing the usage of classical antitumoral agents, corticosteroids, and, importantly, of antibiotics, as well as their waste.

Carotenoids are natural products regulated by the food sector, currently used as feed dyes and as antioxidants in dietary supplements and composing functional foods for human consumption. Of the nearly one thousand carotenoids described to date, only retinoids, derived from beta carotene, have the status of a drug and are regulated by the pharmaceutical sector. In this review, we address a novel field: the transformation of xanthophylls, particularly the highly marketed astaxanthin and the practically unknown bacterioruberin, in therapeutic agents by altering their pharmacokinetics, biodistribution, and pharmacodynamics through their formulation as nanomedicines. The antioxidant activity of xanthophylls is mediated by routes different from those of the classical oral anti-inflammatory drugs such as corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs): remarkably, xanthophylls lack therapeutic activity but also lack toxicity. Formulated as nanomedicines, xanthophylls gain therapeutic activity by mechanisms other than increased bioavailability. Loaded into ad hoc tailored nanoparticles to protect their structure throughout storage and during gastrointestinal transit or skin penetration, xanthophylls can be targeted and delivered to selected inflamed cell groups, achieving a massive intracellular concentration after endocytosis of small doses of formulation. Most first reports showing the activities of oral and topical anti-inflammatory xanthophyll-based nanomedicines against chronic diseases such as inflammatory bowel disease, psoriasis, atopic dermatitis, and dry eye disease emerged between 2020 and 2023. Here we discuss in detail their preclinical performance, mostly targeted vesicular and polymeric nanoparticles, on cellular models and in vivo. The results, although preliminary, are auspicious enough to speculate upon their potential use for oral or topical administration in the treatment of chronic inflammatory diseases.

The anti-inflammatory, antifibrotic and antimicrobial activities of curcumin (CUR) are missed because of its low solubility in aqueous media, low bioavailability, and structural lability upon oral intake. Soft nanoparticles such as nanoliposomes are not efficient as CUR carriers, since crystalline CUR is expelled from them to physiological media. Nanostructures to efficiently trap and increase the aqueous solubility of CUR are needed to improve both oral or nebulized delivery of CUR. Here we showed that SRA1 targeted nanoarchaeosomes (nATC) [1:0.4 w:w:0.04] archaeolipids, tween 80 and CUR, 155 ± 16 nm sized of -20.7 ± 3.3 z potential, retained 0.22 mg CUR ± 0.09 per 12.9 mg lipids ± 4.0 (~600 μM CUR) in front to dilution, storage, and nebulization. Raman and fluorescence spectra and SAXS patterns were compatible with a mixture of enol and keto CUR tautomers trapped within the depths of nATC bilayer. Between 20 and 5 µg CUR/mL, nATC was endocytosed by THP1 and A549 liquid-liquid monolayers without noticeable cytotoxicity. Five micrograms of CUR/mL nATC nebulized on an inflamed air-liquid interface of A549 cells increased TEER, normalized the permeation of LY, and decreased il6, tnfα, and il8 levels. Overall, these results suggest the modified pharmacodynamics of CUR in nATC is useful for epithelia repair upon inflammatory damage, deserving further deeper exploration, particularly related to its targeting ability.