Iontophoretic Delivery of Hyaluronic Acid Nanogel-Loaded Fermented Rice Extract Mitigates Skin Glycation

Int J Nanomedicine. 2025 Sep 18:20:11417-11434. doi: 10.2147/IJN.S523731. eCollection 2025.

Abstract

Purpose: This study aims to evaluate the efficacy of Saccharomyces/Rice Ferment Filtrate (SRFF) in mitigating glycation-related skin aging, specifically focusing on the reduction of advanced glycation end products (AGEs) through improved transdermal delivery using nanotechnology and iontophoresis.

Methods: We developed a hyaluronic acid (HA) nanogel as a carrier for SRFF, which enhances drug delivery efficiency and stability while providing skin protection. Iontophoresis, a non-invasive electrochemical method, was employed to facilitate the transdermal penetration of SRFF into the skin. An ex vivo skin tissue glycation model was established, and immunohistochemistry and tissue mechanics assessments were conducted to analyze the effects of SRFF combined with HA nanogel and iontophoresis.

Results: The combination of SRFF with HA nanogel and iontophoresis significantly reduced the formation of AGEs and mitigated the stiffening effects associated with glycation. The results demonstrated pronounced anti-glycation effects at both the cellular and ex vivo tissue levels. The observed reductions in AGEs and improved skin barrier functionality were likely due to the antioxidant properties of SRFF and its ability to competitively bind to AGEs crosslinking sites.

Conclusion: This study highlights the potential of SRFF, in conjunction with HA nanogels and iontophoresis, as an effective method for anti-glycation treatment, reducing AGE accumulation and alleviating skin yellowing and stiffness. The findings support the development of non-invasive, efficacious strategies for enhancing skin health and counteracting the effects of aging.

Keywords: advanced glycation end products; flexible electrodes; mechanical characterization of skin; natural inhibitors; non-invasive transdermal.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Fermentation
  • Glycation End Products, Advanced* / metabolism
  • Glycosylation / drug effects
  • Humans
  • Hyaluronic Acid* / administration & dosage
  • Hyaluronic Acid* / chemistry
  • Iontophoresis / methods
  • Nanogels / chemistry
  • Oryza* / chemistry
  • Plant Extracts* / administration & dosage
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Skin Aging / drug effects
  • Skin* / drug effects
  • Skin* / metabolism

Substances

  • Hyaluronic Acid
  • Nanogels
  • Glycation End Products, Advanced
  • Plant Extracts
  • Drug Carriers