Some pharmaceutical excipients are able to modify intestinal permeability, thus influencing drug absorption and bioavailability. The effect of four polyols (mannitol, maltitol, sorbitol and xylitol) on the permeability of seven active pharmaceutical ingredients (API), representing different BCS classes (furosemide, amiloride, atenolol, ranitidine, nadolol, L-thyroxine and acyclovir), was investigated using the Caco-2 cell permeability model. Analytical methods for the sensitive polyol and API quantification were developed using Ultra High Performance Liquid Chromatography coupled to triple-quadrupole Mass Spectrometry (UHPLC-QqQ). Apparent permeability coefficients (P_app) were calculated from the measured concentrations in the apical and basolateral compartments. The cell monolayer remained intact throughout the experiment in all trials, neither significant Lucifer Yellow (LY) passage, nor modification of the electrical resistance was detected, demonstrating that no active principle or excipient (or combinations thereof) modulated the paracellular transport. The P_app values for apical to basolateral and basolateral to apical directions of drug + excipient combinations were compared with the Papp values for the drug substance alone. Our results show that mannitol, maltitol, sorbitol and xylitol did not modify the permeability of furosemide, amiloride, atenolol, ranitidine, nadolol, acyclovir and L-thyroxine APIs. Moreover, the presence of polyols did not alter the efflux of the active principle (basolateral to apical).

KLEPTOSE^® CRYSMEB methylated cyclodextrin derivative displays less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases, linked in part to cholesterol complexation and immune response, however, its impact on inflammatory cascade pathways is not clear. Thus, the impact of KLEPTOSE^® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells under physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP^® Diversity PLUS^® panel. Finally, its anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE^® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects that were driven by the inhibition of pro-inflammatory cytokine secretion and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Additionally, it appeared that the mechanism of action of KLEPTOSE^® CRYSMEB seems to not be shared by other well-known anti-inflammatory molecules. Finally, KLEPTOSE^® CRYSMEB may have an anti-inflammatory impact, which could be due to its effect on receptors such as TLR or direct complexation with LPS or PGE2, and conversely, this methylated cyclodextrin could stimulate a pro-inflammatory response involving lipid mediators and on proteins involved in communication with immune cells, probably via interaction with membrane cholesterol.

KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

This study aimed to compare the biological activities of major oxysterols, including 7-ketocholesterol (7KC), 7α-hydroxycholesterol (7α-HC), 7β-hydroxycholesterol (7β-HC), and 27-hydroxycholesterol (27HC), as well as oxidized LDL (oxLDL), in complementary human models representative of the atherosclerotic microenvironment: monocyte-derived macrophages (MΦs), vascular endothelial cells (v-ECs), and vascular smooth muscle cells (v-SMCs) isolated from the carotid artery and abdominal aorta. Cellular responses were strongly dependent on both cell type and vascular territory. Among the oxysterols tested, 7KC exerted the strongest biological effects, markedly reducing cell viability, increasing oxidative stress and apoptosis, promoting endothelial dysfunction, and profoundly altering lipid homeostasis pathways. Spectral Nile Red analysis further revealed distinct patterns of neutral-lipid- and phospholipid-associated fluorescence, indicating oxysterol-specific remodeling of intracellular lipid compartments. In vascular smooth muscle cells, 7KC was associated with increased CD36 expression and reduced ABCA1/ABCG1-mediated cholesterol efflux, whereas macrophages responded predominantly through SREBP1- and NR1H4-associated metabolic reprogramming rather than enhanced lipid uptake. In contrast, oxLDL was the strongest inducer of neutral lipid accumulation and classical foam-cell formation in macrophages. Although 27HC increased intracellular 7KC levels, it induced comparatively limited effects on viability, oxidative stress, and macrophage functions. Moreover, oxLDL promoted a distinct macrophage activation state and altered polarization trajectories depending on the timing of exposure. These findings demonstrate that major oxysterols exert distinct and complementary biological effects across vascular and immune cell populations, highlighting their differential contribution to atherosclerotic plaque development and progression, and support the development of therapeutic approaches targeting multiple oxysterol species rather than a single oxidized cholesterol derivative.

Bio-based succinic acid (bSU) has emerged as a promising mild exfoliating agent, yet its effects on desquamation pathways, barrier-related protein regulation, and irritation potential remain insufficiently characterized in human-relevant skin models. Therefore, this study systematically evaluated bSU against salicylic acid (SA) using reconstructed human epidermis and human skin explants to assess irritation profile and desquamation-related biological responses. Our findings reveal that bSU facilitates controlled corneocyte shedding by modulating the targets LEKTI, KLK, and CDSN. Moreover, bSU demonstrated a favorable ability to maintain physiological skin surface acidity, all while minimizing inflammatory activation. These results position bSU as a balanced exfoliating bioactive that effectively promotes stratum corneum renewal while preserving cutaneous barrier homeostasis, providing mechanistic insights to support its development in advanced mild exfoliation formulations.