Targeting Delivery of Dexamethasone to Inflamed Joints by Albumin-Binding Peptide Modified Liposomes for Rheumatoid Arthritis Therapy

Huan Wang,1,* Rui Gou,2,* Wei Li,2 Zhoujiang Chen,2 Chun Gu,3 Sanjun Shi,4 Liang Zou,2 Hanmei Li2 1Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, People’s Republic of China; 2Key Laboratory of Coarse Cereal Processing (Ministry of Agriculture and Rural Affairs), School of Food and Biological Engineering, Chengdu University, Chengdu, 610106, People’s Republic of China; 3Department of Hepatobiliary & Pancreatic Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 4State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hanmei Li; Liang Zou, Email [email protected]; [email protected]: Delivering the anti-inflammatory dexamethasone in nanoformulations is important for reducing off-target effects when treating rheumatoid arthritis. Nanoformulations can be targeted to sites of inflammation by modifying the nanoparticles with albumin before administration, but such particles can be unstable in vivo.Methods: Here, we have developed and validated an alternative targeting in which dexamethasone-loaded liposomes were modified with a 46-residue peptide called “albumin-binding domain”, such that the liposomes would adsorb endogenous albumin after administration.Results: The resulting liposomes were small (90 nm diameter) and uniformly dispersed, and both X-ray diffraction and differential scanning calorimetry confirmed efficient dexamethasone encapsulation. Functionalizing the liposomes with albumin-binding peptide strongly increased not only their binding to albumin in vitro but also their uptake by RAW264.7 cells in culture. After injection into rats with adjuvant-induced arthritis, the liposomes accumulated and persisted at sites of inflammation, effectively inhibiting joint swelling and reducing the level of the inflammatory factors TNF-α and IL-1β in joints. The liposomes decorated with the albumin-binding peptide did not display obvious hepatotoxicity and did not reduce red and white blood cells number.Discussion: Our results validate modifying liposomes with albumin-binding domain as a way to target them to sites of inflammation for efficient drug delivery against rheumatoid arthritis.Keywords: endogenous albumin, rheumatoid arthritis, liposomes, targeting therapy, dexamethasone