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Dual-Drug Loaded Separable Microneedles for Efficient Rheumatoid Arthritis Therapy
Mengchen An1,2,3, Mengxiao Shi1,2,3, Jingjing Su1,2,3
1Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, No. 100 Science Ave, Zhengzhou 450001, China.
Pharmaceutics
|July 27, 2022
Summary
This study developed microneedles for rheumatoid arthritis treatment, combining interleukin-6 receptor (IL-6R) and tumor necrosis factor-α (TNF-α) inhibitors. This novel approach improved drug delivery and efficacy in mice models.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Rheumatology Research
Background:
- Interleukin-6 receptor (IL-6R) and tumor necrosis factor-α (TNF-α) inhibitors show promise for rheumatoid arthritis (RA) but face challenges with side effects and patient compliance.
- Current treatments necessitate improved drug delivery methods to enhance efficacy and patient adherence.
Purpose of the Study:
- To develop a novel microneedle (MN) system for the co-delivery of tocilizumab (TCZ), an IL-6R inhibitor, and Apt1-67, a TNF receptor 1 inhibitor.
- To achieve differential drug release kinetics (sustained for TCZ, rapid for Apt1-67) for improved therapeutic outcomes in rheumatoid arthritis.
Main Methods:
- Fabrication of separable microneedles (MN) using methacrylate-grafted hyaluronic acid for TCZ (needle tips) and polyvinyl alcohol/polyvinyl pyrrolidone for Apt1-67 (needle bodies).
- Characterization of drug distribution within the MN structure and in vitro/in vivo release studies.
- Evaluation of the therapeutic efficacy of co-delivered TCZ and Apt1-67 via MN in collagen-induced arthritis (CIA) mouse models, comparing it to single-drug MN and subcutaneous injection.
Main Results:
- Successful fabrication of MN with distinct compartments for TCZ and Apt1-67, demonstrating expected drug distribution.
- Confirmation of differential release profiles: sustained release of TCZ from needle tips and rapid release of Apt1-67 from needle bodies upon skin insertion.
- In vivo studies showed that the combined TCZ/Apt1-67@MN treatment significantly inhibited bone erosion and alleviated RA symptoms in CIA mice, outperforming single-drug MN and conventional subcutaneous injection.
Conclusions:
- The developed microneedle system offers a novel and effective approach for the co-delivery of drugs with different release characteristics for rheumatoid arthritis treatment.
- This strategy demonstrates superior therapeutic efficacy compared to single-drug treatments and subcutaneous injections, highlighting its potential to improve patient compliance and drug effectiveness.
