HA20, a Broad-Molecular-Weight Hyaluronic Acid Complex, Supports Transepidermal Bioavailability and Multi-Stress Barrier Protection in Human Skin Models
It is suggested that HA20 supports barrier resilience mainly through improved transepidermal delivery and ECM or barrier-repair responses.
Abstract
Hyaluronic acid (HA) is widely used in skincare, but its efficacy varies with molecular weight (MW), affecting its skin penetration and activity. This study examined whether HA20, a broad-MW HA complex (weight-average MW: 188 kDa, 10–1000 kDa), improves skin absorption and shields human skin models from environmental stress. HA transepidermal bioavailability, extracellular-matrix responses, glyoxal-induced Nε-(carboxymethyl)lysine (CML), UVA-induced mitochondrial membrane potential (MMP) loss, Th2 cytokine-induced markers, and dryness-induced barrier changes were assessed in reconstructed human epidermis, dermal fibroblasts, and epidermal keratinocytes. HA20 exhibited greater apparent permeation detectable by ELISA at all time points during the 24 h RHE assay compared to high-MW HA. In fibroblasts, 0.05% HA20 increased type I collagen secretion from 535.20 to 585.47 pg/mL and elastin from 8.68 to 9.24 pg/mL, reduced CML fluorescence to 70.13% of the glyoxal control, and increased MMP-associated fluorescence from 58.76% in the UVA model group to 298.86%. In keratinocytes, 0.1% HA20 reduced IL-4/IL-13-induced NELL2 and CAII expression. Under acute dryness, HA20 maintained stratum corneum morphology and altered transcriptomic signatures related to epidermal differentiation, extracellular matrix organization, and barrier-associated genes, including KRT37, COL7A1, ACER2, and SPRR1A. These findings suggest that HA20 supports barrier resilience mainly through improved transepidermal delivery and ECM or barrier-repair responses.
Background Skin aging involves intrinsic chronological aging and extrinsic photoaging, characterized by impaired barrier function, extracellular matrix (ECM) degradation, and chronic inflammation. Methods This study evaluated anti-aging efficacy and mechanisms of ergothioneine (EGT), collagen peptides (CP) and sodium hyaluronate (NaHA) using an ex vivo human skin model and a clinical trial. Results Ex vivo results showed that the EGT+CP+NaHA triple combination (TC) attenuated UV-induced epithelial thinning and collagen fiber disruption. Mechanistically, TC enhanced antioxidant capacity by up-regulating Nrf2 and SOD2 expression, modulated the senescence-associated secretory phenotype (SASP) via restoring TGF-β1 and suppressing IL-1α, IL-6, and MMP1 levels, and preserved ECM integrity by reversing reductions in collagen I, III, IV, VII, XVII, and hyaluronic acid (HA) contents. Clinically, oral TC to Chinese women improved skin hydration, elasticity, and barrier function, while reducing the number, depth, area, and volume of crow's feet wrinkles, nasolabial folds and marionette lines. Conclusion These findings demonstrate that TC exerts multifaceted anti-aging effects by targeting oxidative stress, inflammatory pathways, and ECM homeostasis, providing a scientific basis for the development of novel oral nutricosmetics for facial skin anti-aging.
Zhiqin Zhou, Lingling Zhao, Lei Chen et al.· Frontiers in Nutrition· 0 citations
Hyaluronic acid (HA)-based hydrogels are widely used as wound-healing materials and topical delivery systems because of their excellent biocompatibility, water retention capacity, and ability to promote cell migration. However, HA is prone to oxidative chain scission, which reduces molecular weight and compromises formulation stability and functional performance. This study evaluated the feasibility of ergothioneine (EGT) as a candidate antioxidant stabilizing excipient in a model HA-based wound-healing material. CCK-8 assays assessed the biocompatibility of EGT in L929 mouse fibroblasts after 24 h of exposure, and a stress-screening framework including Fenton oxidation, high-temperature/high-humidity treatment, light exposure, and quiescent storage at 4 °C was established. The results showed that Fenton oxidation markedly induced HA degradation, whereas EGT incorporation effectively protected HA structural integrity under oxidative stress. Cell scratch assays further demonstrated that EGT did not interfere with the ability of HA to promote cell migration. EGT may serve as a candidate antioxidant stabilizing excipient for HA-based wound-healing materials, improving HA structural and material stability under oxidative challenge while preserving HA-associated cell-migration function.
Tian-Yu Ma, Shuangshuang Qi, Jun-Kai Liu et al.· Polymers· 0 citations
Collagen is widely used in the cosmetics industry as an active ingredient in skin-care formulations due to its biocompatibility, biodegradability, low antigenicity, and high biological activity. As a natural humectant, collagen binds water molecules within the skin, reduces transepidermal water loss, and helps maintain skin elasticity and hydration. Despite its broad application, the influence of collagen on epithelial ion transport remains insufficiently understood. This study evaluated the effect of a gel containing triple-helical collagen on sodium and chloride ion transport in the isolated rabbit skin. The collagen gel was applied to 25 skin specimens for 24 h and compared with 30 untreated control specimens. Electrophysiological analyses included measurements of transepithelial electrical potential (PD), electrical resistance (R), and potential changes during stimulation (PDmin and PDmax). Collagen gel significantly decreased R compared with control tissues, indicating altered tissue permeability. Collagen gel-treated tissues also exhibited a significantly more electropositive PDmin than controls, whereas PDmax values remained comparable between groups, suggesting that electrophysiological responsiveness was maintained under the experimental conditions. The observed electropositive shift in PDmin may reflect altered sodium ion transport. Whether these electrophysiological changes are associated with changes in tissue hydration requires direct investigation.
Dominika Dąbrowska-Wisłocka, Aleksandra Kalinoska, O. Zavyalova et al.· Cosmetics· 0 citations
Background: Effective topical management of sensitive skin remains challenging because inadequate cutaneous delivery limits the therapeutic performance of many anti-inflammatory agents. Glycyrrhetinic acid (GA) possesses well-recognized anti-inflammatory and barrier-protective activities, yet its clinical potential is constrained by poor aqueous solubility and inefficient skin delivery. This study aimed to develop a hyaluronic acid (HA)-engineered ethosomal system to enhance the local delivery and therapeutic efficacy of GA for sensitive skin. Methods: HA-coated GA-loaded ethosomes (HAGA-ETs) were prepared by electrostatic adsorption of HA onto a cationic ethosomal template. The physicochemical properties, release behavior, storage stability, skin retention, cellular uptake, and biological activities of HAGA-ETs were systematically evaluated using TNF-α/IFN-γ-stimulated HaCaT cells and an SLS-induced 3D reconstructed skin model. Results: HAGA-ETs exhibited a mean particle size of 140.1 nm, encapsulation efficiency exceeding 95%, sustained drug release, and good storage stability. Compared with Free-GA and unmodified ethosomes, HAGA-ETs showed improved cytocompatibility, enhanced skin retention, greater keratinocyte uptake, and stronger anti-inflammatory activity. HA pre-saturation attenuated the enhanced cellular uptake of HAGA-ETs, supporting the involvement of HA receptor-mediated cellular interaction. HAGA-ETs also more effectively restored barrier-related markers, suppressed hyper-reactivity- and allergy-associated mediators, and inhibited the activation of MAPK/NF-κB, JAK1/STAT1, and TRPV1-related signaling pathways in both cellular and 3D skin models. Conclusions: HA surface engineering effectively improved the topical delivery and local therapeutic efficacy of GA by enhancing skin retention and keratinocyte interaction. HAGA-ETs represent a promising nanoplatform for the local management of sensitive skin.
Skin aging is a complex biological process driven by collagen degradation and oxidative damage, often exacerbated by UV exposure. While resveratrol is a premier antioxidant for anti-aging, its topical efficacy is historically limited by poor water solubility and weak skin penetration. This study addresses these barriers by developing optimized polyethylene glycol-based liposomes (PEG-liposomes) as novel deformable liposome derivative. The uncoated vesicles demonstrated high stability and uniformity, with a size of 320.17 ± 0.25 nm and a zeta potential of -35.2 ± 0.4 mV. By coating these vesicles with 0.1% hyaluronic acid (HA), successful surface functionalization and improved size stability was achieved. Ex vivo and confocal studies confirmed that these PEG-liposomes successfully reached the deep dermis; notably, a sequential application strategy of the coated and uncoated PEG-liposomes showed that uncoated vesicles could transiently disrupt lipid structures to facilitate deeper penetration for the HA-coated versions. When integrated with micro-needling via a derma roller, the system triggered significant collagen remodeling and a surge in antioxidant enzymes like SOD, while simultaneously reducing oxidative stress markers such as MDA, MMP-1, and the aging indicator beta-galactosidase. The cooperative effect of this dual-vesicle system not only restored the structural integrity of the dermal-epidermal junction but also significantly outperformed existing commercial resveratrol products. Our findings demonstrate that this novel PEG-liposomal system provides a transformative approach to deep-tissue rejuvenation. Through its unique synergistic mechanism with micro-needling, it achieves biological remodeling and dermal restoration that surpasses the efficacy of current market-leading standards.
Merna Zoweil, Dina Aboushady, Ahmed S. Kamel et al.· European journal of pharmace...· 0 citations
Abstract Skin photoaging, predominantly caused by chronic ultraviolet B (UVB) exposure, is characterized by oxidative stress, collagen degradation, and disruption of the skin barrier. Deer placenta polypeptides (DPP) are rich in bioactive amino acids (AAs); however, their antioxidant and dermo-protective effects remain insufficiently elucidated, and their topical application is limited by enzymatic instability and poor transdermal permeability. To overcome these limitations, we developed a liposome–hydrogel composite delivery system to enhance the stability, skin penetration, and bioactivity of DPP. DPP obtained via enzymatic hydrolysis exhibited a favorable AA profile, free radical–scavenging activity, and a low molecular weight distribution (3–14 kDa). DPP-loaded liposomes (DPP-LIP) demonstrated high encapsulation efficiency, uniform nanosize, and effective preservation of bioactivity. Incorporation of DPP-LIP into a sodium alginate (SA) hydrogel yielded a composite formulation (DPP-LIP-SA) with sustained-release properties and a 2.7-fold enhancement in transdermal permeation. In a UVB-induced photoaging mouse model, topical administration of DPP-LIP-SA markedly alleviated oxidative stress, inflammatory responses, DNA damage, and extracellular matrix degradation. Mechanistically, DPP-LIP-SA treatment activated the Nrf2/HO-1 antioxidant pathway, inhibited TLR4/MyD88/NF-κB-mediated inflammatory signaling, reduced reactive oxygen species accumulation and lipid peroxidation, and restored extracellular matrix homeostasis by promoting collagen synthesis while suppressing MMP-mediated collagen degradation. Collectively, these findings identify DPP as a potent bioactive peptide resource with intrinsic antioxidant and reparative properties and demonstrate that integration of nanocarriers with hydrogel matrices substantially enhances dermal bioavailability. This composite delivery platform shows strong potential as a peptide-based topical strategy for preventing and treating skin photoaging.
Yifan Liu, Kejia Chen, Jin Pei et al.· Drug Delivery· 0 citations
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