Macrophage-Targeted Berberine-Loaded β-Glucan Nanoparticles Enhance the Treatment of Ulcerative Colitis

Yuying Xu,1,* Jintao Huang,2,* Yapei Fan,1 Haiyue Long,1 Minting Liang,1 Qunjie Chen,1 Zhiping Wang,2 Chaoxi Wu,1 Yifei Wang1 1Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaoxi Wu; Yifei Wang, Email chaoxiw@gmail.com; twang-yf@163.comAim: This study focuses on constructing of an anti-inflammatory drug delivery system by encapsulation of berberine in the β-glucan nanoparticles and evaluates its effect on treating ulcerative colitis.Methods: β-Glucan and the anti-inflammatory drug berberine (BER) are self-assembled into nanoparticles to construct a drug delivery system (GLC/BER). The interaction between the drug and the carrier was characterized by circular dichroism, ultraviolet-visible spectroscopy, and dynamic light scattering. The anti-inflammatory effect of the GLC/BER was evaluated through a lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammation model and a sodium sulfate (DSS)-induced C57BL/6 mouse ulcerative colitis model.Results: The GLC/BER nanoparticles have a particle size of 80– 120 nm and a high encapsulation efficiency of 37.8± 4.21%. In the LPS-induced RAW264.7 macrophage inflammation model, GLC/BER significantly promoted the uptake of BER by RAW264.7 cells. RT-PCR and ELISA assay showed that it could significantly inhibit the inflammatory factors including IL-1β, IL-6 and COX-2. Furthermore, GLC/BER shows inhibiting effect on the secretion of pro-inflammatory factors such as IL-1β and IL-6, down-regulating the production of nitrite oxide; in animal studies, GLC/BER was found to exert a relieving effect on mice colitis.Conclusion: The study found that GLC/BER has an anti-inflammatory effect in vitro and in vivo, and the GLC carrier improves the potency and bioavailability of BER, providing a new type of nanomedicine for the treatment of colitis.Keywords: β-glucan, chiral, drug carrier, immunoregulation, anti-inflammation