Reprogramming M1-to-M2 Phenotype to Alleviate Inflammation: Using Liposomal Curcumin as a Tool to Redefine Macrophage Functionality

Abstract

The versatile nature of macrophages and their ability to switch between various activation states plays a pivotal role in both promoting and inhibiting inflammatory processes. In pathological inflammatory conditions, classically activated M1 macrophages are often associated with initiating and maintaining inflammation, while alternatively activated M2 macrophages are linked to the resolution of chronic inflammation. Achieving a favorable equilibrium between M1 and M2 macrophages is crucial for mitigating inflammatory environments in pathological conditions. Polyphenols are known to have strong inherent antioxidative capabilities, and curcumin has been found to reduce macrophage inflammatory reactions. However, its therapeutic efficacy is compromised due to its poor bioavailability. The present study aims to harness the properties of curcumin by loading it in nanoliposomes and enhancing the M1-to-M2 macrophage polarization. A stable liposome formulation was achieved at 122.1 ± 0.08 nm, and a sustained kinetic release of curcumin was observed within 24 h. The nanoliposomes were further characterized using TEM, FTIR, and XRD, and the morphological changes in macrophage cells, RAW264.7, were observed in SEM, indicating a distinct M2-type phenotype after the treatment with liposomal curcumin. ROS may partially control macrophage polarization and be observed to decrease after treatment with liposomal curcumin. The nanoliposomes were able to successfully internalize in the macrophage cells, and an enhanced expression of ARG-1 and CD206 with a decrease in iNOS, CD80, and CD86 levels suggested the polarization of LPS-activated macrophages toward the M2 phenotype. Also, liposomal curcumin treatment dose-dependently inhibited TNF-α, IL-2, IFN-γ, and IL-17A at secretory levels and simultaneously increased the levels of cytokines like IL-4, IL-6, and IL-10.

Engineered Robust Hydrophobic/Hydrophilic Nanofibrous Scaffolds with Drug-Eluting, Antioxidant, and Antimicrobial Capacity

“…Therefore, these fabrics can deliver curcumin as a medicinal herb to the injured tissue in a controlled manner so that it allows for effective inhibition of the protein denaturation even at relatively low drug concentrations. The increased bioavailability of the complexed drug can potentially alleviate chronic inflammation and mitigate oxidative stress, 63 preventing the loss of tissue function and delayed wound recovery.…”

Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment

“…Mechanistically, curcumin may reduce reactive oxygen species (ROSs) and reduce lipid peroxidation by acting as an antioxidant and/or by modulating signal transduction and the expression of genes that are relevant for inflammation and lipid homeostasis [ 58 , 59 ]. Liposomal curcumin facilitates the polarization of pro-inflammatory M1 to anti-inflammatory M2 macrophages, which is relevant for the treatment of a variety of inflammatory conditions [ 60 , 61 ]. Further, curcumin can modulate cellular lipid homeostasis, leading to the inhibition of lipid accumulation and reduced inflammatory gene expression, steatohepatitis, and macrophage foam cell formation, which are relevant for cardiovascular disease [ 10 , 58 , 59 , 62 , 63 , 64 ].…”