PLGA nanoparticles loaded with the antimicrobial peptide LL37 accelerated wound closure in cell studies while providing controlled peptide release — a promising platform for treating chronic and drug-resistant wound infections.
102.3 nm nanoparticles via microfluidicsMicrofluidic fabrication produced significantly smaller, more uniform, and more stable nanoparticles (102.3 nm) compared to conventional nanoprecipitation (189.3 nm), with superior peptide release profiles for wound healing applications.
What the researchers found
Palmitoylated LL37 antimicrobial peptide encapsulated in PLGA nanoparticles showed enhanced stability and controlled release. Microfluidic fabrication produced superior nanoparticles compared to nanoprecipitation — smaller (102.3 nm vs 189.3 nm), more uniform, more stable, and with prolonged peptide release. The loaded nanoparticles enhanced keratinocyte uptake and significantly accelerated fibroblast-mediated wound closure. Proteomic analysis of the nanoparticle protein corona showed enrichment in coagulation, inflammation modulation, and extracellular matrix remodeling proteins.
Why it matters
LL37, the only human cathelicidin antimicrobial peptide, is a promising alternative to antibiotics for treating chronic and drug-resistant wound infections. But free LL37 degrades rapidly and is toxic at high concentrations. This nanoparticle delivery system solves both problems — protecting the peptide while releasing it in a controlled manner that accelerates wound healing and fights infection simultaneously.
How the study worked
Palmitoylated LL37 was encapsulated in FDA-approved PLGA nanoparticles using two fabrication methods: nanoprecipitation and microfluidics. Nanoparticles were characterized for size, uniformity, stability, and peptide release kinetics. Biological activity was tested through keratinocyte uptake assays and fibroblast wound closure (scratch) assays. Proteomic analysis of the nanoparticle protein corona (proteins that adsorb to the surface in biological fluids) was performed to understand how the nanoparticles interact with the wound environment.
Who was studied
In vitro cell-based experiments using human keratinocytes and fibroblasts
What this study cannot tell us
All experiments were conducted in vitro using cell cultures — no in vivo animal wound healing studies were performed. The proteomic protein corona analysis suggests the nanoparticles may modulate the wound environment, but this has not been confirmed in living tissue. The antimicrobial activity of the encapsulated LL37 against specific wound pathogens is not reported in the abstract. Scale-up feasibility from microfluidics to manufacturing is not addressed.
How to read the evidence
This is a preclinical in vitro study focusing on nanoparticle design, characterization, and cell-based functional testing. While the results are promising for peptide delivery technology, all experiments were conducted in cell culture without in vivo validation, placing this at an early stage of development.
When this study was published
Published in 2025, this is a very recent study contributing to the active field of antimicrobial peptide delivery systems for wound healing applications.
The bigger picture
Antibiotic resistance is making chronic wound infections increasingly difficult to treat. Antimicrobial peptides like LL37 represent a fundamentally different approach to infection control — one that bacteria are much less likely to develop resistance against. The challenge has been delivering these fragile peptides effectively. This nanoparticle platform addresses the key barriers of stability and controlled release, potentially enabling AMP-based wound therapies that combine infection fighting with accelerated tissue repair.
Questions still open
- How do LL37-loaded PLGA nanoparticles perform in animal wound healing models with established bacterial infections?
- Does the protein corona that forms on these nanoparticles meaningfully enhance wound healing in vivo, or is it primarily an in vitro phenomenon?
- Can this nanoparticle platform be adapted for other antimicrobial peptides beyond LL37?
Common questions
What is LL37 and why is it important for wound healing?
Why can't LL37 just be applied directly to wounds?
Read the original research
Lipidized LL37-loaded PLGA nanocarriers: Bioengineered peptide delivery systems for enhanced wound healing.
International journal of pharmaceutics, 677, 125668
Citation
De Soricellis, Chiara; Laigle, Chloé; Spinelli, Lucio; Monti, Maria Chiara; Amante, Chiara; Russo, Paola; Aquino, Rita Patrizia; Rousselle, Patricia; Lollo, Giovanna; Del Gaudio, Pasquale. (2025). Lipidized LL37-loaded PLGA nanocarriers: Bioengineered peptide delivery systems for enhanced wound healing.. International journal of pharmaceutics, 677, 125668. https://doi.org/10.1016/j.ijpharm.2025.125668