Phytoactive-Loaded Lipid Nanocarriers for Simvastatin Delivery: A Drug Repositioning Strategy Against Lung Cancer

Area of Science:

• Nanomedicine
• Drug Delivery
• Oncology

Background:

• Drug repurposing offers new therapeutic avenues for existing medications.
• Simvastatin (SV), a lipid-lowering drug, exhibits anticancer potential but faces limitations in solubility and side effects.
• Novel delivery systems are needed to enhance SV's efficacy and overcome its limitations in lung cancer therapy.

Purpose of the Study:

• To enhance simvastatin (SV) delivery and efficacy against lung cancer cells.
• To formulate bioactive lipid nanoparticles using plant-derived monoterpenes as nanostructuring and anticancer agents.
• To evaluate the potential of these nanoparticles for lung cancer treatment through drug repurposing.

Main Methods:

• Lipid nanoparticles (LNPs) were prepared via ultrasonication and characterized for size, PDI, and zeta potential.
• Monoterpenes (linalool, limonene, 1,8-cineole) or Crodamol® were used as liquid lipids for nanoparticle formulation.
• Encapsulation efficiency, release profiles, stability, biocompatibility, cytotoxicity, and anticancer effects were assessed.

Main Results:

• LNPs demonstrated high stability with sizes ranging from 94.2 to 144.0 nm and PDI < 0.3.
• Simvastatin (SV) encapsulation significantly enhanced cytotoxicity against A549 lung cancer cells, particularly in NLC/LN/SV formulation.
• NLC/LN/SV exhibited sustained SV release (>95% EE over 72h), excellent biocompatibility, efficient cellular uptake, and induced G0/G1 cell cycle arrest and apoptosis.

Conclusions:

• NLC/LN/SV nanoparticles represent a promising nanocarrier for simvastatin (SV) repurposing in lung cancer therapy.
• The formulation combines enhanced anticancer activity, improved biocompatibility, and sustained drug release.
• This approach offers a potential strategy for overcoming SV's limitations and improving lung cancer treatment outcomes.