Macrophage repolarization using CD44-targeting hyaluronic acid-polylactide nanoparticles containing curcumin

Area of Science:

• Biomaterials Science
• Nanotechnology
• Immunology

Background:

• Macrophage polarization plays a critical role in inflammatory diseases.
• Modulating macrophage phenotype from pro-inflammatory (M1) to anti-inflammatory (M2) is a therapeutic strategy.
• Curcumin, a natural compound, possesses anti-inflammatory properties but faces bioavailability challenges.

Purpose of the Study:

• To evaluate curcumin encapsulated in CD44-targeting hyaluronate-polylactide (HA-PLA) nanoparticles (NPs) for modulating macrophage polarity.
• To assess the efficacy of nano-formulated curcumin in shifting M1 macrophages to an M2 phenotype.
• To investigate the potential of this formulation as a therapeutic approach for inflammatory conditions.

Main Methods:

• Characterization of HA-PLA NPs using 1HNMR, FTIR, DLS, and FE-SEM.
• Assessment of nanoparticle cytotoxicity and cellular uptake via MTT assay and confocal microscopy.
• Quantification of M1 (iNOS-2) and M2 (Arg-1) markers, and pro-inflammatory cytokines using real-time PCR.

Main Results:

• Curcumin-loaded HA-PLA NPs exhibited a spherical shape with an average diameter of 102.5 nm and demonstrated high cellular uptake.
• The nano-formulation showed significantly lower toxicity to peritoneal macrophages compared to free curcumin.
• Nano-formulated curcumin effectively reduced M1 marker (iNOS-2) expression and increased M2 marker (Arg-1) expression, suppressing pro-inflammatory cytokines.

Conclusions:

• CD44-targeting HA-PLA nanoparticles effectively deliver curcumin to modulate macrophage polarity.
• The nano-formulation demonstrates reduced toxicity and enhanced anti-inflammatory effects compared to free curcumin.
• Curcumin-loaded HA-PLA NPs represent a promising platform for the treatment of inflammatory diseases.