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Resveratrol nanocrystals based dissolving microneedles with highly efficient for rheumatoid arthritis

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Abstract

Rheumatoid arthritis (RA) is a common immune disease characterized mainly by erosive arthritis with extensive clinical sequelae. Resveratrol (Res) has pharmacological effects in the treatment of RA, but it has not been widely used in the clinic due to its poor water solubility and low bioavailability. In this study, a drug delivery system (Res-NC MNs) of dissolved microneedles (MNs) loaded with Res nanocrystals (NC) was designed for the treatment of RA. Res-NC MNs can improve the drawbacks of long-term oral drug delivery with toxic side effects and low compliance associated with intra-articular drug delivery. In this study, Res-NC was prepared by media milling and loaded into soluble microneedles prepared from hyaluronic acid (HA) by vacuum casting for the treatment of RA. HA has high mechanical strength and can penetrate the cuticle layer of the skin for effective drug delivery. In in vivo pharmacodynamic experiments, Res-NC MNs achieved better therapeutic efficacy in the treatment of RA compared with oral Res. These findings suggest that Res-NC MNs may be an effective and promising drug delivery strategy for the treatment of RA.

Graphical Abstract

Schematic diagram of resveratrol nanocrystals microneedles for rheumatoid arthritis

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Neither the entire paper nor any part of its content has been published or has been accepted elsewhere. It is not being submitted to any other journal. Hope this study can be suitable for the journal.

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Funding

All authors acknowledge financial support from Natural Science Foundation of Shandong Province (No. ZR2019ZD24, ZR2019YQ30); Taishan Scholar Foundation of Shandong Province (No. qnts20161035); Graduate Innovation Foundation of Yantai University, GIFYTU.

Author information

Authors and Affiliations

  1. Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, School of Pharmacy, Yantai University, Yantai, 264005, PR China

    Ningning Diao, Wenxin Wang, Min Cao, Xiaowei Liu, Weili Yang, Yuxin Cao, Tianying Sun, Huijie Pei & Daquan Chen

  2. Yantai Food and Drug Inspection and Testing Center, Yantai, 264035, PR China

    Yan Liu

  3. College of Marine Life Science, Ocean University of China, Yushan 10 Road, Qingdao, 266003, PR China

    Chunjing Guo

Authors
  1. Ningning Diao
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  2. Yan Liu
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  3. Wenxin Wang
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  4. Min Cao
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  5. Xiaowei Liu
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  6. Weili Yang
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  7. Yuxin Cao
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  8. Tianying Sun
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  9. Huijie Pei
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  10. Chunjing Guo
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  11. Daquan Chen
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Contributions

Ningning Diao: Contributed to the conception of the study, experimented. Yan Liu: Revised the manuscript. Wenxin Wang and Min Cao: Visualization, Data curation. Xiaowei Liu and Weili Yang: Visualization, Data curation. Tianying Sun and Huijie Pei: Performed the data analyses and wrote the manuscript. Chunjing Guo: Helped perform the analysis with constructive discussions. Daquan Chen: Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Writing-review & editing.

Corresponding authors

Correspondence to Chunjing Guo or Daquan Chen.

Ethics declarations

Ethics approval and consent to participate

All experiments were conducted by the ARRIVE Guidelines and were approved by the Animal Ethics Committee of Yantai University (Ethical Annotation License Number: YTU20220923). Male Sprague-Dawley rats (180 ∼ 200 g) were purchased from Jinan Pengyue Experimental Animal Breeding Co., Ltd. (Shandong, China). All animals have free access to food and water and are housed at a temperature of 22 ± 1℃, relative humidity of 50 ± 1%, and a light/dark cycle of 12/12 h. Before administration, the rats were anesthetized with intra-peritoneal injection of anesthetics (80 mg/kg ketamine and 4.5 mg/kg xylazine) while monitoring body temperature with a feedback-conditioned heating pad. Rats were euthanized by intraperitoneal injection of excessive pentobarbital sodium. The study does not involve human subjects.

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All authors have read and agreed to the published version of the manuscript.

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The authors declare no competing interests.

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Diao, N., Liu, Y., Wang, W. et al. Resveratrol nanocrystals based dissolving microneedles with highly efficient for rheumatoid arthritis. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01581-2

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  • DOI: https://doi.org/10.1007/s13346-024-01581-2

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