Lipidized LL37-loaded PLGA nanocarriers: Bioengineered peptide delivery systems for enhanced wound healing

Area of Science:

• Biomaterials Science
• Nanotechnology
• Wound Healing Research

Background:

• Antimicrobial peptides (AMPs) like LL37 are potential alternatives to antibiotics for wound infections.
• Clinical use of AMPs is hindered by instability and toxicity.
• Poly(lactic-co-glycolic acid) (PLGA) nanoparticles offer a delivery platform for enhanced AMP stability and controlled release.

Purpose of the Study:

• To encapsulate palmitoylated LL37 (LL37(P)) into PLGA nanoparticles using nanoprecipitation and microfluidics.
• To compare the efficacy of microfluidics versus nanoprecipitation for nanoparticle fabrication.
• To evaluate the therapeutic potential of LL37(P)-loaded PLGA nanoparticles in wound healing.

Main Methods:

• Fabrication of PLGA nanoparticles encapsulating LL37(P) via nanoprecipitation and microfluidics.
• Characterization of nanoparticle size, uniformity, and stability.
• Assessment of LL37(P) release kinetics.
• Evaluation of nanoparticle uptake by keratinocytes and fibroblasts.
• Analysis of wound closure acceleration in vitro.
• Proteomic analysis of the nanoparticle-protein corona.

Main Results:

• Microfluidic fabrication yielded uniform, smaller nanoparticles (102.3 nm) with improved stability and prolonged LL37(P) release compared to nanoprecipitation (189.3 nm).
• LL37(P)-loaded nanoparticles enhanced keratinocyte uptake and accelerated fibroblast-mediated wound closure.
• Proteomic analysis indicated nanoparticle involvement in coagulation, inflammation modulation, and ECM remodeling.

Conclusions:

• PLGA nanoparticles fabricated via microfluidics provide a stable platform for AMP delivery in wound healing.
• LL37(P)-loaded PLGA nanocarriers show therapeutic potential for infection control and regenerative medicine.
• Nanoparticle-protein corona plays a role in modulating the wound healing microenvironment.