Nano-in-micro alginate/chitosan hydrogel via electrospray technology for orally curcumin delivery to effectively alleviate ulcerative colitis

[Display omitted] •A nanoparticles-in-microparticles system was fabricated by electrospray technology for curcumin colon-targeting oral delivery in ulcerative colitis treatment.•Encapsulation in hydrogel microparticles could avoid the immature drug release of nanoparticles in the upper gastrointestinal tract.•Curcumin-loaded in the nanoparticles-in-microparticles systems were apt to reach colitis lesion and enter into inflammatory macrophages to suppress inflammation. Although nano-systems can promote the cellular internalization, polymeric nanoparticles (NPs) are easily to be destroyed or eliminated in the gastrointestinal tract, which leads to premature drug release or insufficient colonic accumulation. A novel oral nano-in-micro system for the efficient colonic delivery of curcumin (Cur) was developed in this study, in which the hyaluronic acid (HA)/zein complex NPs loading Cur were embedded in alginate/chitosan hydrogel microparticles (Cur@NMPs) with the electrospray technology. The Cur@NMPs showed uniform-sized sphere with an average size of 218.36 ± 10 μm, encapsulating Cur@HA/zein NPs with the average size of 148.64 ± 3.21 nm. Cur in NMPs showed the sustained drug-release profiles in simulated gastric fluid, whereas it showed the rapid release in simulated colonic fluid. Mediated by the HA-CD44 receptor recognition, Cur@HA/zein NPs had the increased cellular uptake efficiency in macrophages. Furthermore, NMPs had the significant colon-retention and bio-adhesiveness capacity in colon tissues. As expected, the oral administration of Cur@NMPs significantly mitigated colitis symptoms in DSS-induced UC mice by inhibiting TLR4/NF-κB pathway. The above results can provide a useful drug delivery strategy for Cur in the treatment of UC by retaining the advantages of nano- and micro-scaled carriers.