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

Abstract

The aim of this study was to evaluate the efficiency of using a natural substance, curcumin, encapsulated in CD44-targeting hyaluronate-polylactide (HA-PLA) nanoparticles (NPs) for the modulation of macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype. For this purpose, the characterization of the NPs was monitored using HNMR, FTIR, DLS and FE-SEM. The effects of curcumin-encapsulated HA-PLA NPs on the viability of LPS/IFN-γ stimulated peritoneal macrophages were determined using MTT assay. The cellular uptake of free curcumin and nano-formulated curcumin was assessed using confocal microscopy. Also, the expression levels of iNOS-2 (M1 marker), Arg-1 (M2 marker) and also pro-inflammatory cytokines were measured by real-time PCR. Data showed that the nano-formulated curcumin with spherical shape, an average diameter of 102.5 nm and high cellular uptake was significantly less toxic to peritoneal macrophages. Furthermore, the nano-formulated curcumin effectively indicated a reduction in iNOS-2 and an increase in Arg-1 levels than free curcumin. The change in macrophage phenotype by curcumin-encapsulated HA-PLA NPs could suppress the inflammation in LPS/IFN-γ stimulated macrophages as evidenced by a major reduction in pro-inflammatory cytokines. Conclusively, the results suggested that the curcumin formulation with CD44-targeting HA-PLA NPs might be a promising platform for the treatment of inflammatory diseases.

Spotlight on 17‐AAG as an Hsp90 inhibitor for molecular targeted cancer treatment

“…In recent years, advances in nanomaterials‐based drug delivery carriers have paved the way for overcoming these obstacles (Deldar, Zarghami, Pilehvar‐Soltanahmadi, Dadashpour, & Zarghami, ; Farajzadeh et al., ; Montazeri et al., ). The main advantages of nanocarriers for anticancer drugs include improved therapeutic effect, extended half‐life in the bloodstream, increased water solubility, improved stability, selective delivery to specific site, and decreased hepatotoxicity (Firouzi‐Amandi et al., ; Jalilzadeh‐Tabrizi et al., ; Nejati‐Koshki, Mortazavi, Pilehvar‐Soltanahmadi, Sheoran, & Zarghami, ; Zamani, Pilehvar‐Soltanahmadi, Alizadeh, & Zarghami, ).…”

Enhanced anti-proliferative and pro-apoptotic effects of metformin encapsulated PLGA-PEG nanoparticles on SKOV3 human ovarian carcinoma cells

“…Use of polymeric nanoparticles (NPs) such as polylactic acid-co-glycolic acid-polyethylene glycol (PLGA-PEG) to the delivery of anti-cancer agents may have a great potential to overcome these limitations. As a drug delivery system, polymeric NPs exhibit some advantages including elevated drug stability, high delivery capability, the feasibility of delivering both hydrophilic and hydrophobic drugs, improved shelf life, and the possibility of different administration routes [13][14][15].…”

Targeted Drug Delivery via the Use of ECM-Mimetic Materials

“…Hyaluronic acid has also been utilized to target CD44 receptors overexpressed in macrophages as a strategy for the treatment of inflammatory disease. Pilehvar-Soltanahmadi and co-workers reported hyaluronic acid-conjugated polylactide nanoparticles encapsulated curcumin delivered to macrophage to achieve the modulation of macrophage polarity from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype (Farajzadeh et al, 2018). The modification of ECM polysaccharides accomplishes the delivery of drugs at the target sites where their receptors are highly expressed.…”