Effect of particle size on the cellular uptake and anti-inflammatory activity of oral nanotherapeutics.

To elucidate the impacts of particle size on the cell internalization and anti-inflammatory activity of oral nanotherapeutics, curcumin (CUR)-loaded polymeric nanoparticles (NPs) with different particle sizes were fabricated. The obtained NPs with particle sizes (185-884 nm) and negative zeta potentials (approximately -25 mV) had desirable CUR loading amounts (5.1-6.1 %) and high CUR encapsulation efficiency (73.2-89.6 %). In vitro cellular uptake assays revealed that the cell internalization efficiencies of NPs were increased with the increase of their particle sizes, and NPs (900) showed the highest phagocytosis efficiency in macrophages among all the tested NPs. Importantly, NPs (900) exhibited significantly stronger capability to downregulate the production of the main pro-inflammatory cytokines from macrophages when they were compared with NPs (200) and NPs (500). Further animal studies suggested that oral administration of hydrogel (chitosan and alginate)-embedding NPs (900) could efficiently accumulate in colitis tissue in a manner that was comparable to that of NPs (200) and NPs (500) and could achieve the best treatment efficacy against ulcerative colitis (UC). Collectively, these findings can serve as a guideline for the rational design of nanotherapeutics with desirable accumulation profiles in colitis tissue, maximized cellular uptake efficiency in macrophages, and good therapeutic outcomes against UC.