Nanoencapsulation enhanced the performance of β-carotene for ameliorating inflammation in patient-derived organoids

This study aims to develop a nanocarrier system for the oral delivery of β-Carotene (BC) (as a model therapeutic agent) and to test its efficacy in ameliorating inflammation in an ulcerative colitis (UC) patient-derived organoid. BC was encapsulated in a zein protein nano-cage surface-functionalized with pectin and polyethyleneglycol (PEG). The nanoencapsulated BC (nBC) was characterized for physicochemical properties (size, charge, surface chemistry) and functional properties (radical scavenging, mucoadhesion and penetration, release in simulated digestive fluids). Further, we evaluated the performance of nBC in ameliorating inflammation in Caco-2 and UC patient-derived organoid models. nBC achieved 75% encapsulation efficiency with improved stability and functional properties when compared to free BC. The nanocarrier was non-cytotoxic and improved mucoadhesion, mucopenetration, and the anti-inflammatory potential of BC. In UC organoids, nBC suppressed dextran sulfate sodium (DSS)-induced TNF-α and IL-8 production by approximately 70% and 31%, respectively, which was significantly higher than free BC at comparable concentrations. The protein-polymer nanoencapsulation strategy showed promise in protecting BC and overcoming intestinal mucus barriers for an improved anti-inflammatory effect in the organoid model. Further studies using animal models are warranted for establishing pharmacokinetics, tissue distribution, and therapeutic index of orally delivered nBC.