Bioactive nanocapsules based on lychee-like bilayer structure for synovitis treatment

Abstract

Osteoarthritis (OA), as a degenerative disease, often necessitates intra-articular administration to alleviate pain. Synovial inflammation represents an important pathological factor in the development of OA. ZIF-8 (a type of Zeolitic imidazolate frameworks), a newly developed drug carrier, has garnered significant attention due to its high drug loading capacity and favorable biocompatibility. However, pH-sensitive burst drug release in inflammatory environments hampered its clinical application. To overcome this limitation, we have engineered a novel lychee-like double-layered bioactive nanocapsule, with ZIF-8 serving as the core and a bioactive amorphous sol as the outer shell, facilitated by Zn ion and Si–O coordination. The amorphous sol not only inhibits the rapid degradation of ZIF-8 in inflammatory conditions, preventing quick drug release, but also enhances the immunomodulatory capabilities of the functional carrier. Remarkably, our studies reveal that, in addition to sustained drug release, the synergistic effect of the functional carrier and anti-inflammatory drugs can regulate inflammation-induced lymphatic abnormalities. This is manifested by the suppression of macrophage secretion of excessive VEGF-C and iNOS, thereby modulating lymphatic density and restoring normal lymphatic rhythmic function. These findings indicate that such pathology-adaptive functional carriers possess superior drug release control and immunomodulatory potential compared to traditional carriers, presenting a promising innovative material for synovitis treatment.