Targeting the resolution pathway of inflammation using Ac2–26 peptide-loaded PEGylated lipid nanoparticles for the remission of rheumatoid arthritis

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint inflammation and immune dysfunction. Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications, the low responsiveness of RA patients and undesired systemic toxicity are...

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Bibliographic Details
Published in:Asian journal of pharmceutical sciences 2021-07, Vol.16 (4), p.483-493
Main Authors: Qin, Xianyan, He, Liming, Fan, Donghao, Liang, Wenlang, Wang, Qin, Fang, Jiyu
Format: Article
Language:English
Subjects:
Ac2–26 peptide
Drug delivery
Original Research Paper
Pegylated lipid nanoparticles
Pro-resolving therapy
Rheumatoid arthritis
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Summary:Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint inflammation and immune dysfunction. Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications, the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems. Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation. Ac2–26, a 25-amino acid peptide derived from Annexin A (a pro-resolving mediator), has shown good efficacy in the treatment of inflammatory disorders. However, the low bioavailability of Ac2–26 peptides hinders their efficacy in vivo. In this paper, we formed PEGylated lipid nanoparticles (LDNPs) by the co-assembly of l-ascorbyl palmitate (L-AP) and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE-PEG2k) to encapsulate and deliver Ac2–26 peptides to the arthritic rats. They showed good stability and biocompatibility. After being intravenously administrated, Ac2–26 peptide-loaded PEGylated lipid nanoparticles (ADNPs) showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites. In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology. Therefore, the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment. The fabrication of ADNPs and their in vivo performances in arthritic rats. [Display omitted]
ISSN:1818-0876
2221-285X
DOI:10.1016/j.ajps.2021.03.001