Affiliation:
1. Department of Rheumatology and Immunology Institute of Translational Medicine Nanjing Drum Tower Hospital Clinical Medical College of Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing 210096 China
2. State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
Abstract
Rheumatoid arthritis (RA) is one of the leading causes of disability due to the autoimmune destruction of synovial joints. Great efforts have been put into developing multifunctional drug delivery systems for delaying the progression of RA. Herein, a novel locally injectable, hierarchically structured delivery system with a hyaluronic acid (HA) microparticle and an MTX‐conjugated nanoparticle for promoted RA treatment is proposed. In this system, MTX is chemically grafted onto a peptide dendrimer‐based nanoparticle (G‐MTX). These nanoparticles are encapsulated inside HA microparticles (H‐G‐MTX) using microfluidics to realize the system. The G‐MTX can be released from the degradable HA microparticles in the acidic environment of inflamed RA joints. As the G‐MTX shows an enhanced intracellular delivery of the conjugated MTX, the H‐G‐MTX can reverse the dominant macrophage phenotype from M1 to M2. Through a collagen‐induced arthritis (CIA) rat model, the great therapeutic outcomes of this hierarchically structured delivery system are demonstrated, including inflammation reduction, cartilage protection, and bone mineral density promotion. These results indicate that the proposed hierarchical delivery system has potential clinical value in the treatment of RA and other diseases.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Jiangsu Provincial Key Research and Development Program
Natural Science Foundation of Jiangsu Province
Subject
General Earth and Planetary Sciences,General Environmental Science