Nanoemulsions Embedded in Alginate Beads as Bioadhesive Nanocomposites for Intestinal Delivery of the Anti-Inflammatory Drug Tofacitinib

Oraladministration of nanoparticles (NPs) is a promising strategyto overcome solubility and stability issues of many active compounds.However, this route faces major obstacles related to the hostile gastrointestinal(GI) environment, which impairs the efficacy of orally administerednanomedicines. Here, we propose nanocomposites as a promising approachto increase the retention time of NPs in the intestinal tract by usingbio- and mucoadhesive matrixes able to protect the cargo until itreaches the targeted area. A microfluidic-based approach has beenapplied for the production of tailored nanoemulsions (NEs) of about110 nm, used for the encapsulation of small hydrophobic drugs suchas the anti-inflammatory JAK-inhibitor tofacitinib. These NEs provedto be efficiently internalized into a mucus-secreting human intestinalmonolayer of Caco-2/HT29-MTX cells and to deliver tofacitinib to subepithelialhuman THP-1 macrophage-like cells, reducing their inflammatory response.NEs were then successfully encapsulated into alginate hydrogel microbeadsof around 300 mu m, which were characterized by rheological experimentsand dried to create a long-term stable system for pharmaceutical applications.Finally, ex vivo experiments on excised segmentsof rats ' intestine proved the bioadhesive ability of NEs embeddedin alginate hydrogels compared to free NEs, showing the advantagethat this hybrid system can offer for the treatment of intestinalpathologies.