# Perillaldehyde-Encapsulated Lipid Nanoparticle Hydrogel for Enhanced Wound Healing, Improved Stability and Biocompatibility

**Authors:** Jiansang Wulu, Wenfang Jin, Sirong Peng, Qing Yang, Jing Li, Zhifeng Zhang

PMC · DOI: 10.3390/ijms27042061 · International Journal of Molecular Sciences · 2026-02-23

## TL;DR

A new wound dressing using perillaldehyde in lipid nanoparticles within a hydrogel improves healing, stability, and safety compared to traditional methods.

## Contribution

A novel nano-in-hydrogel platform for controlled delivery of perillaldehyde with enhanced stability and biocompatibility.

## Key findings

- PAH-L showed uniform size, high encapsulation efficiency, and colloidal stability.
- PAH-L-G demonstrated sustained release and improved wound healing in a rat model.
- The dressing showed low hemolysis and high fibroblast viability in compatibility tests.

## Abstract

Volatile phytochemicals such as perillaldehyde (PAH) exhibit antimicrobial and anti-inflammatory activities relevant to wound repair; however, topical use is limited by volatility, chemical instability, and potential irritation associated with burst exposure. Here, we developed a nano-in-hydrogel dressing by encapsulating PAH into lipid nanoparticles (PAH-L) and incorporating them into a carbomer hydrogel (PAH-L-G). PAH-L showed a uniform nanoscale size distribution, high encapsulation efficiency, and good colloidal stability. After gel incorporation, PAH-L-G formed an interconnected porous network with rapid swelling and a more sustained release profile than free PAH or PAH-L. Hemocompatibility and cytocompatibility assays indicated low hemolysis and high fibroblast viability. In a full-thickness rat wound model, PAH-L-G accelerated wound closure and improved histological regeneration without obvious local irritation. Overall, the lipid-nanoparticle-in-hydrogel strategy stabilizes PAH and enables controlled topical delivery, supporting PAH-L-G as a promising wound dressing platform.

## Linked entities

- **Chemicals:** perillaldehyde (PubChem CID 16441)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Pah (phenylalanine hydroxylase) [NCBI Gene 24616], Pecam1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 29583] {aka CD31, Pecam}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}
- **Diseases:** Hemolysis (MESH:D006461), bacterial (MESH:D001424), Cytotoxicity (MESH:D064420), Swelling (MESH:D004487), infected (MESH:D007239), Skin injury (MESH:D000069836), inflammation (MESH:D007249), injury to (MESH:D014947)
- **Chemicals:** cholesterol (MESH:D002784), Lecithin (MESH:D054709), triethanolamine (MESH:C009546), Reactive oxygen species (MESH:D017382), aldehyde (MESH:D000447), PAH (MESH:C033342), PBS (MESH:D007854), KBr (MESH:C039004), eosin (MESH:D004801), TBARS (MESH:D017392), copper (MESH:D003300), ABTS (MESH:C002502), paraformaldehyde (MESH:C003043), Lipid (MESH:D008055), BHT (MESH:D002084), free fatty acids (MESH:D005230), chloroform (MESH:D002725), carbomer 940 (MESH:C006903), terpenoids (MESH:D013729), water (MESH:D014867), CCK-8 (MESH:D012844), DPPH (MESH:C004931), acetonitrile (MESH:C032159), ester (MESH:D004952), fatty acids (MESH:D005227), C (MESH:D002244), potassium persulfate (MESH:C009007), peroxide (MESH:D010545), nitrogen (MESH:D009584), Cyclodextrin (MESH:D003505), MDA (MESH:D015104), phosphotungstic acid (MESH:D010772), Carbomer (MESH:C479038), hematoxylin (MESH:D006416), paraffin (MESH:D010232), A734 (-), H&amp;E (MESH:D006371), gold (MESH:D006046), COO (MESH:C041069), methanol (MESH:D000432)
- **Species:** Perilla frutescens (beefsteak-mint, species) [taxon 48386], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038), L929 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_AR58), NCTC clone 929, L cell, L-929 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0462)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941144/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941144/full.md

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Source: https://tomesphere.com/paper/PMC12941144