PEG-Lipid-PLGA Hybrid Particles for Targeted Delivery of Anti-Inflammatory Drugs

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Developing targeted drug delivery systems is crucial for enhancing therapeutic efficacy and reducing side effects.
• Hybrid nanoparticles (HNPs) offer a versatile platform for combining different materials to achieve specific functionalities.
• Functionalized lipid shells on nanoparticles can mediate targeted cellular uptake and drug release.

Purpose of the Study:

• To design and characterize hybrid nanoparticles (HNPs) with functionalized lipid shells for targeted drug delivery.
• To evaluate the cellular uptake and drug delivery efficiency of HNPs in human monocyte-derived macrophages (MDMs).
• To investigate the potential of HNPs loaded with an anti-inflammatory drug for inhibiting 5-lipoxygenase (5-LOX) activity.

Main Methods:

• HNPs were synthesized with a PLGA core and a lipid shell functionalized with PEG-Lipid conjugates (-RGD, -cRGD, -NH2, -COOH).
• Nanoparticle characterization included size, stability, and degradation studies.
• Cellular uptake was assessed in MDMs using flow cytometry (FC) and confocal laser scanning microscopy (CLSM).
• Drug delivery efficiency was evaluated by measuring the inhibition of 5-LOX product formation using BRP-201 loaded HNPs.

Main Results:

• HNPs functionalized with -RGD, -cRGD, -NH2, and -COOH groups were successfully synthesized and characterized.
• HNP-COOH and HNP-RGD demonstrated superior uptake in MDMs compared to other formulations.
• The HNP-COOH/RGD (2:1) hybrid nanoparticle formulation showed the highest inhibition of 5-LOX product formation, indicating efficient drug delivery.

Conclusions:

• Functionalized hybrid nanoparticles represent a promising platform for targeted drug delivery to macrophages.
• The surface functionalization of HNPs significantly influences their cellular uptake and therapeutic efficacy.
• The HNP-COOH/RGD formulation exhibits excellent potential for delivering anti-inflammatory drugs to treat conditions involving 5-LOX pathway activation.