Hyaluronic acid-functionalized nanoparticles for ulcerative colitis-targeted therapy: a comparative study of oral administration and intravenous injection†

Targeted delivery of anti-inflammatory drugs to macrophages has attracted great attention for selectively alleviating the symptoms of ulcerative colitis (UC), while minimizing adverse effects. Herein, we aimed to compare the in vivo pharmacokinetics and therapeutic outcomes of macrophage-targeted nanoparticles (NPs) via oral administration and intravenous injection. Polymeric NPs were employed to load an anti-inflammatory drug (curcumin, CUR), followed by surface functionalization with hyaluronic acid (HA). The resulting HA-CUR-NPs had an average diameter of 281 nm and a negatively charged surface. These NPs showed excellent biocompatibility and a significantly higher cell internalization efficiency in RAW 264.7 macrophages compared with their counterparts (carboxymethyl cellulose-functionalized CUR-encapsulated NPs, CUL-CUR-NPs). Moreover, HA-CUR-NPs exhibited a dramatically stronger capacity to inhibit the mRNA expression levels of the typical pro-inflammatory cytokines from lipopolysaccharide-stimulated macrophages compared with CUL-CUR-NPs. In vivo experiments revealed that HA-CUR-NPs after i.v. injection could improve the pharmacokinetics of CUR, and that it showed much better UC therapeutic outcomes compared with the oral administration way. Collectively, in comparison with HA-CUR-NPs (oral), HA-CUR-NPs (i.v.) possess a higher CUR delivery efficiency to the colitis mucosa, which can be developed as an efficient platform for UC treatment.