Targeting Delivery of Dexamethasone to Inflamed Joints by Albumin-Binding Peptide Modified Liposomes for Rheumatoid Arthritis Therapy
Huan Wang, Rui Gou, Wei Li, Zhoujiang Chen, Chun Gu, Sanjun Shi, Liang Zou, Hanmei Li
Abstract
Introduction: 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.