Abstract
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.
Highlights
Inhaled medication capable of inducing alveolar epithelial repair, may be more efficient than oral medication to impair the advance of fibrotic changes Here we found that besides of displaying anti-inflammatory activity, nebulized CUR loaded nanoarchaeosomes rebuilt the barrier properties of an air–liquid interface (ALI) in vitro model made of A549 cells, potentially constituting novel lung epithelial repairing agents
Hoechst 33342, CellMask Deep Red Plasma membrane stain, 5-(and-6)-chloromethyl20,70 -dichlorodihydrofluorescein diacetate, acetyl ester, Lucifer Yellow (LY), Roswell Park Memorial Institute 1640 (RPMI), Modified Eagle Medium (MEM), penicillin-streptomycin sulphate, glutamine, sodium pyruvate and trypsin/ethylenediamine tetra acetic acid were from Life Technologies (NY, USA), fetal bovine serum (FBS) was from
The order and fluidity of the nanovesicles bilayer with or without CUR were assessed by determining the Laurdan generalized polarization (GP) and fluorescence anisotropy (FA)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Different from liposomes, the nanoarchaeosomes prepared with archaeolipids from H. tebenquichense are naturally targeted to cells expressing SRA1 [21] Such as Kupffer cells, splenic, thymic, and alveolar macrophages [22–24], endothelial cells lining the liver and adrenal sinusoids [22,23] and on the high endothelial cells of postcapillary venules in the lymph nodes [25]. Inhaled medication capable of inducing alveolar epithelial repair, may be more efficient than oral medication to impair the advance of fibrotic changes Here we found that besides of displaying anti-inflammatory activity, nebulized CUR loaded nanoarchaeosomes rebuilt the barrier properties of an air–liquid interface (ALI) in vitro model made of A549 cells, potentially constituting novel lung epithelial repairing agents
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