A Nanoliposome Platform Co-Delivery of Hydroxypinacolone Retinoate and Carnosine for Enhanced Epidermal/Dermal Delivery and Multi-Functional Anti-Aging Efficacy

  • Pharmaceutics. 2026 Apr 8;18(4):454. doi: 10.3390/pharmaceutics18040454.
Siyuan Chen  1 ,  Lihao Gu  2 ,  Ruili Zhao  2 ,  Lihua Zhang  2 ,  Lina Yao  2 ,  Jingning Shen  2 ,  Dan Luo  3  4 ,  Xi Wang  4 ,  Dan Chen  4 ,  Si Zhao  4 ,  Hong Zhou  5 ,  Wei Liu  3  6
Affiliations
  • 1. Research Institute for Biomaterials, Tech Institute for Advanced Materials Bioinspired Biomedical Materials & Devices Center, College of Materials Science and Engineering, Jiangsu Collaborative Innovation Center for Advanced Inorganic Function Composites, Suqian Advanced Materials Industry Technology Innovation Center, Nanjing Tech University, Nanjing 211816, China.
  • 2. Osman Biological Co., Ltd., Huzhou 313200, China.
  • 3. National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430075, China.
  • 4. Wuhan Bestcarrier Biotechnology Co., Ltd., Wuhan 430074, China.
  • 5. USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
  • 6. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
PMID: 42076106 DOI: 10.3390/pharmaceutics18040454
Abstract

Background: Effective Anti-aging requires dual strategies to stimulate regeneration and counteract damage. While the combination of hydroxypinacolone retinoate (HPR) and carnosine (CA) holds great promise, their effectiveness is hampered by instability and poor skin penetration. Methods: To overcome these challenges, this study developed HPR and CA co-encapsulated nanoliposomes (HC-NLPs) via high-pressure homogenization as an advanced epidermal/dermal delivery system. Results: HC-NLPs markedly improved skin retention of HPR (58.97%) and CA (111.36%) compared to the free combination (Free-HC). In cellular studies, HC-NLPs displayed excellent biocompatibility and demonstrated a 4.7-fold higher cellular uptake. This led to enhanced proliferative (EdU positive rate increased by 78.32%) and migratory (wound closure improved by 31.5%) capacities. Moreover, HC-NLPs effectively reinforced multiple skin-protective processes associated with aging, including enhanced resistance to oxidative and glycation-induced damage, suppressed inflammatory responses, and strengthened cellular barrier integrity. In 3D skin models, HC-NLPs promoted Collagen deposition and improved tissue morphology compared to Free-HC. Their superior in vivo antioxidant and Anti-aging effects were further validated in Zebrafish assays. HC-NLPs effectively co-deliver HPR and CA, markedly improving their stability, skin penetration, and cellular internalization. Conclusions: The formulation demonstrates comprehensive pro-regenerative, anti-inflammatory, antioxidative, and anti-glycation effects, representing a promising nano-delivery strategy for advanced Anti-aging skincare.

Keywords
Nanoliposomes; anti-aging; carnosine; co-delivery; epidermal/dermal delivery; hydroxypinacolone retinoate.
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