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Coordinating Macrophage Targeting and Antioxidation by Injectable Nanocomposite Hydrogel for Enhanced Rheumatoid
Houqin Liu1, Yingke Liu2, Zhipeng Tian1
1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.
ACS Applied Materials & Interfaces
|July 10, 2024
Summary
A novel injectable hydrogel effectively treats rheumatoid arthritis (RA) by delivering anti-inflammatory and antioxidant drugs directly to joint tissues, reducing inflammation and bone erosion.
Area of Science:
- Biomaterials Science
- Immunology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) involves immune cell infiltration and oxidative stress, leading to joint damage.
- Proinflammatory factors and reactive oxygen species (ROS) from immune cells exacerbate RA pathology.
- Current RA treatments require improved targeted anti-inflammatory and antioxidant strategies.
Purpose of the Study:
- To develop a thermosensitive injectable hydrogel for coordinated anti-inflammatory and antioxidant therapy in RA.
- To create a drug delivery system targeting macrophages and alleviating oxidative stress in the joint microenvironment.
- To evaluate the therapeutic efficacy of the developed hydrogel in a rat model of RA.
Main Methods:
- Development of a thermosensitive injectable hydrogel (Dex-DSLip/Cro@Gel) encapsulating dexamethasone (Dex)-loaded liposomes (Dex-DSLip) and crocin I (Cro).
- Dex-DSLip modified with dextran sulfate (DS) to target macrophages via scavenger receptor A (SR-A).
- Intra-articular injection of the hydrogel in a rat model of RA and assessment of inflammatory markers and joint damage.
Main Results:
- The hydrogel demonstrated sustained release of Dex and Cro, prolonging drug retention time.
- Intra-articular injection significantly reduced inflammatory factor expression in RA rat ankle joints.
- Marked alleviation of joint erythema and bone erosion was observed, indicating therapeutic benefits.
Conclusions:
- The developed thermosensitive injectable hydrogel synergistically combines anti-inflammatory and antioxidant effects.
- Targeting the joint microenvironment and macrophages offers a novel therapeutic approach for RA.
- The hydrogel shows potential for long-term RA treatment with mitigated bone erosion.
