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Nanomedicine-based combination of dexamethasone palmitate and MCL-1 siRNA for synergistic therapeutic efficacy against rheumatoid arthritis

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A Correction to this article was published on 28 May 2024

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Abstract

The main aim of this research was to design a MCL-1 siRNA and dexamethasone (DEX)-loaded folate modified poly(lactide-co-glycolide) (PLGA)-based polymeric micelles with an eventual goal to improve the therapeutic outcome in the rheumatoid arthritis (RA). Polymeric micelles encapsulating the MCL-1 siRNA and DEX was successfully developed and observed to be stable. Physicochemical characteristics such as particle size and particle morphology were ideal for the systemic administration. Folate-conjugated DEX/siRNA-loaded polymeric micelles (DS-FPM) significantly lowered the MCL-1 mRNA expression compared to either DEX/siRNA-loaded polymeric micelles (DS-PM) or free siRNA in Raw264.7 cells and macrophage cells suggesting the importance of targeted nanocarriers. Most importantly, DS-FPM exhibited a greatest decrease in the hind paw volume with lowest clinical score compared to any other treated group indicating a superior anti-inflammatory activity. DS-FPM showed significantly lower levels of the TNF-α and IL-1β compared to AIA model and free groups. The folate receptor (FR)-targeting property of DS-FPM has been demonstrated to be a promising delivery platform for the effective delivery of combination therapeutics (siRNA and DEX) toward the treatment of rheumatoid arthritis.

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All data are made available with the article.

Change history

Abbreviations

DEX:

Dexamethasone

DS-FPM:

DEX/siRNA-loaded folate-conjugated polymeric micelles

DS-PM:

DEX/siRNA-loaded polymeric micelles

FR:

Folate receptors

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Yantaishan Hospital, Yantai, 264000, Shandong, China

    Yanmei Li, Shitong Wei, Yonghua Sun, Shihua Zong & Yameng Sui

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  1. Yanmei Li
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Correspondence to Yanmei Li.

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All animal experiments were approved by the Animal Ethical Committee of the Yantaishan hospital, YanTai. Reporting was in compliance with Animal Research: Reporting In Vivo Experiments (ARRIVE 2.0) guidelines).

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Li, Y., Wei, S., Sun, Y. et al. Nanomedicine-based combination of dexamethasone palmitate and MCL-1 siRNA for synergistic therapeutic efficacy against rheumatoid arthritis. Drug Deliv. and Transl. Res. 11, 2520–2529 (2021). https://doi.org/10.1007/s13346-021-01037-x

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