Liposomal Helix aspersa Snail Mucus: A Biomacromolecular Platform for Attenuating Chronological Skin Aging Through Modulation of miR-34a-Associated Senescence and Extracellular Matrix Remodeling

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Abstract
Chronological skin aging is a complex biological process characterized by progressive collagen degradation and cellular senescence. Among the molecular regulators implicated in these hallmarks, miR-34a has emerged as a critical mediator linking inflammation and senescence pathways. Consequently, this study aimed to investigate the anti-aging potential of Helix aspersa snail mucus, with particular emphasis on its modulation of miR-34a-associated molecular mechanisms, and to explore liposomal encapsulation as a strategy to improve its topical performance and user acceptability. Snail mucus was collected and characterized using LC–ESI–QTOF–MS/MS, while its antioxidant activity was assessed by DPPH and FRAP assays. Afterward, mucus-loaded liposomes were developed and optimized. Aged mice were assigned to control aged, Lipo, free mucus, and Lipo-mucus groups, alongside a young control group. Anti-aging efficacy was evaluated through wrinkle grading, skin moisture determination, histological examination, and collagen assessment by Masson’s trichome staining. miR-34a-5p, its target genes, and related aging-associated genes were also determined, followed by upstream regulatory network prediction using X2Kweb. The optimized formulation exhibited nanoscale particle size, high encapsulation efficiency, enhanced skin retention, and improved spreadability. Compared with free mucus, Lipo-mucus significantly increased the epidermal and dermal deposition of total protein and allantoin. Both treatments exerted remarkable anti-aging effects, evidenced by improved skin architecture and enhanced collagen deposition. These effects were associated with modulation of the miR-34a-5p-driven senescence hub. Collectively, liposomal encapsulation enhanced the cutaneous delivery, cosmetic properties, and anti-aging efficacy of H. aspersa mucus, supporting its potential as a mechanism-based cosmeceutical intervention for chronological skin aging.

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