Multifunctional Hyaluronic Acid-Modified Pterostilbene Nanoliposomes for Enhanced Dermal Delivery and Extracellular Matrix Protection.
- 1Meyer Bio-Medicine Co., Ltd., Jinan 250022, China.
- 2Shandong Meimao Pharmaceutical Co., Ltd., Jinan 250022, China.
- 3National Glycoengineering Research Center, Shandong University, Jinan 250100, China.
Abstract
Background: Skin aging involves extracellular matrix (ECM) deterioration, including collagen loss and disrupted glycosaminoglycan and proteoglycan homeostasis. Pterostilbene (PTE) has antioxidant and anti-inflammatory activity, but its topical use is limited by poor aqueous solubility and limited skin delivery. We developed hyaluronic acid (HA)-modified, PTE-loaded nanoliposomes (HA-LP-PTE) and evaluated their association with dermal fibroblasts, retention in skin, and effects on ECM-related responses. Methods: HA-LP-PTE was prepared by high-pressure microfluidization and assessed for size, morphology, zeta potential, and encapsulation efficiency. Fluorescence microscopy was used to examine fibroblast-associated fluorescence of FITC-labeled HA-LP-PTE and non-HA-modified PTE-loaded liposomes (LP-PTE). Skin retention was assessed using Franz diffusion cells. ECM-related changes were analyzed in UV-irradiated ex vivo skin and fibroblasts using staining techniques and RT-qPCR. Results: HA-LP-PTE had a mean diameter of 55.44 ± 0.81 nm, a polydispersity index of 0.120 ± 0.009, and an encapsulation efficiency of 99.34 ± 0.51%. At 4 h, fibroblast-associated fluorescence was higher than with LP-PTE (p = 0.040) and was reduced by free HA or incubation at 4 °C. After 12 h, dermal PTE retention was 4.08-fold higher than free PTE and 1.74-fold higher than LP-PTE. HA-LP-PTE increased all six ECM components examined. Chondroitin sulfate and perlecan met the Q criterion for synergy, and several ECM synthesis-related genes were upregulated. Conclusions: HA modification improved PTE delivery beyond liposomal encapsulation alone, with greater fibroblast-associated fluorescence and higher PTE retention in viable skin than LP-PTE. ECM and gene-expression findings also indicated matrix-related activity. HA-LP-PTE may enhance topical PTE delivery and attenuate UV-induced ECM loss.
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BibTeX
@article{wang2026multifunctional,
title = {{Multifunctional Hyaluronic Acid-Modified Pterostilbene Nanoliposomes for Enhanced Dermal Delivery and Extracellular Matrix Protection.}},
author = {Zheng Wang and Yumei Fan and Peixue Ling},
journal = {Pharmaceutics},
year = {2026},
month = oct,
doi = {10.3390/pharmaceutics18101313},
url = {https://europepmc.org/article/MED/42942843},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multifunctional Hyaluronic Acid-Modified Pterostilbene Nanoliposomes for Enhanced Dermal Delivery and Extracellular Matrix Protection.
AU - Zheng Wang
AU - Yumei Fan
AU - Peixue Ling
PY - 2026
DA - 2026/10/16
JO - Pharmaceutics
DO - 10.3390/pharmaceutics18101313
UR - https://europepmc.org/article/MED/42942843
AB - Background: Skin aging involves extracellular matrix (ECM) deterioration, including collagen loss and disrupted glycosaminoglycan and proteoglycan homeostasis. Pterostilbene (PTE) has antioxidant and anti-inflammatory activity, but its topical use is limited by poor aqueous solubility and limited skin delivery. We developed hyaluronic acid (HA)-modified, PTE-loaded nanoliposomes (HA-LP-PTE) and evaluated their association with dermal fibroblasts, retention in skin, and effects on ECM-related responses. Methods: HA-LP-PTE was prepared by high-pressure microfluidization and assessed for size, morphology, zeta potential, and encapsulation efficiency. Fluorescence microscopy was used to examine fibroblast-associated fluorescence of FITC-labeled HA-LP-PTE and non-HA-modified PTE-loaded liposomes (LP-PTE). Skin retention was assessed using Franz diffusion cells. ECM-related changes were analyzed in UV-irradiated ex vivo skin and fibroblasts using staining techniques and RT-qPCR. Results: HA-LP-PTE had a mean diameter of 55.44 ± 0.81 nm, a polydispersity index of 0.120 ± 0.009, and an encapsulation efficiency of 99.34 ± 0.51%. At 4 h, fibroblast-associated fluorescence was higher than with LP-PTE (p = 0.040) and was reduced by free HA or incubation at 4 °C. After 12 h, dermal PTE retention was 4.08-fold higher than free PTE and 1.74-fold higher than LP-PTE. HA-LP-PTE increased all six ECM components examined. Chondroitin sulfate and perlecan met the Q criterion for synergy, and several ECM synthesis-related genes were upregulated. Conclusions: HA modification improved PTE delivery beyond liposomal encapsulation alone, with greater fibroblast-associated fluorescence and higher PTE retention in viable skin than LP-PTE. ECM and gene-expression findings also indicated matrix-related activity. HA-LP-PTE may enhance topical PTE delivery and attenuate UV-induced ECM loss.
SN - 1999-4923
ER -