A multifunctional composite hydrogel as an intrinsic and extrinsic coregulator for enhanced therapeutic efficacy for psoriasis
Jiangmei Xu, Hao Chen, Zhaoyou Chu, Li Zhu, Benjin Chen, Jianan Sun, Lai Wei, Yan Ma, Yulong He, Haisheng Qian, Fei Wang, Yunsheng Xu
Abstract
BACKGROUND: Psoriasis is a chronic relapsing immunological skin disease characterized by multiple cross-talk inflammatory circuits which are relevantly associated with abnormal cross-reactivity between immune cells and keratinocytes (KCs). It may be inadequate to eradicate complicated pathogenesis only via single-mode therapy. To provide optimal combinatory therapeutics, a nanocomposite-based hydrogel was constructed by loading methotrexate (MTX) into ZnO/Ag to realize combined multiple target therapy of psoriasis. RESULTS: In this composite hydrogel, ZnO hybrid mesoporous microspheres were utilized both as drug carriers and reactive oxygen species (ROS)-scavenging nanoparticles. A proper amount of Ag nanoparticle-anchored ZnO nanoparticles (ZnO/Ag) was functionalized with inherent immunoregulatory property. The experiments showed that ZnO/Ag nanoparticles could exhibit a self-therapeutic effect that was attributed to reducing innate cytokine profiles by inactivating p65 in proinflammatory macrophages and abrogating secretion of adaptive cytokines in KCs by downregulating ROS-mediated STAT3-cyclin D1 signaling. A preferable antipsoriatic efficacy was achieved via topical administration of this hydrogel on the imiquimod (IMQ)-induced psoriasis mice model, demonstrating the superior transdermal delivery and combined enhancement of therapeutic efficacy caused by intrinsic nanoparticles and extrinsic MTX. CONCLUSION: This composite hydrogel could serve as a multifunctional, nonirritating, noninvasive and effective transcutaneous nanoagent against psoriasis.