A holistic QBD approach to design galactose conjugated PLGA polymer and nanoparticles to catch macrophages during intestinal inflammation

Abstract

Recruited macrophages in inflammation attract various ligand-receptor drug delivery approaches. Galactose bound nanocarriers are promising to catch macrophages because of surface-expressed macrophage galactose type-lectin-C (MGL-2) receptor. The present study reported fabrication of galactose conjugated PLGA (GAL-PLGA) polymer and nanoparticles under quality by design (QBD) approach to investigate macrophages targeting potential at inflamed intestine. GAL-PLGA nanoparticles were fabricated through O/W emulsion-evaporation method under QBD approach and Box-Behnken design. Obtained GAL-PLGA nanoparticles have optimum particle size (~118 nm), drug entrapment (87%) and zeta potential (-9.5). TGA, XPRD and FTIR confirmed stability and negate drug-polymer interactions. Further, nanoparticles have considerable hemocompatibility, biocompatibility and cellular uptake; macrophage uptake was inhibited by D-galactose confirming involvement of MGL-2. Moreover, drug retention studies in the DSS-colitis model provide background for potential of nanoparticles to target and reside inflamed intestine. It is concluded that GAL-PLGA nanoparticles are suitable platform to target macrophages at the inflamed intestine through oral route.

Keywords: C-type lectins; GAL-PLGA nanoparticles; Inflammation; MGL-2 receptor; Macrophage targeting; Quality by design (QBD).