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Neutrophil-Mediated Delivery of Dexamethasone Palmitate-Loaded Liposomes Decorated with a Sialic Acid Conjugate for Rheumatoid Arthritis Treatment

  • Ling Hu
  • Xiang Luo
  • Songlei Zhou
  • Jingyang Zhu
  • Mingyue Xiao
  • Cong Li
  • Huangliang Zheng
  • Qiujun Qiu
  • Chaoyang Lai
  • Xinrong Liu
  • Yihui DengEmail author
  • Yanzhi SongEmail author
Research Paper

Abstract

Purpose

The aim of this research was to design dexamethasone palmitate (DP) loaded sialic acid modified liposomes, with the eventual goal of using peripheral blood neutrophils (PBNs) that carried drug-loaded liposomes to improve the therapeutic capacity for rheumatoid arthritis (RA).

Methods

A sialic acid – cholesterol conjugate (SA-CH) was synthesized and anchored on the surface of liposomal dexamethasone palmitate (DP-SAL). The physicochemical characteristics and in vitro cytotoxicity of liposomes were evaluated. Flow cytometry and confocal laser scanning microscopy were utilized to investigate the accumulation of liposomes in PBNs. The adjuvant-induced arthritis was adopted to investigate the targeting ability and anti-inflammatory effect of DP loaded liposomes.

Results

Both DP-CL and DP-SAL existed an average size less than 200 nm with remarkably high encapsulation efficiencies more than 90%. In vitro and in vivo experiments manifested SA-modified liposomes provided a reinforced accumulation of DP in PBNs. As well, DP-SAL displayed a greater degree of accumulation in the joints and a stronger anti-inflammatory effect in terms of RA suppression.

Conclusions

SA-modified liposomal DP was a promising candidate for RA-targeting treatment through the neutrophil-mediated drug delivery system.

Keywords

L-selectin peripheral blood neutrophils rheumatoid arthritis rheumatoid arthritis-targeting treatment sialic acid-cholesterol conjugate 

Abbreviations

CCK8

Cell Counting Kit-8

CLSM

Confocal laser scanning microscopy

DiR

1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide

DP

Dexamethasone palmitate

EDC

N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

ELISA

Enzyme linked immunosorbent assay

FCM

Flow cytometry

FITC

Fluorescein isothiocyanate

HSPC

Hydrogenated soy phosphatidylcholine

NHS

N-hydroxy-succinimide

PBNs

Peripheral blood neutrophils

RA

Rheumatoid arthritis

SA-CH

A sialic acid-cholesterol conjugate

TNF

Tumor-necrosis factor

Notes

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ling Hu
  • Xiang Luo
  • Songlei Zhou
    • 1
  • Jingyang Zhu
    • 1
  • Mingyue Xiao
    • 1
  • Cong Li
    • 1
  • Huangliang Zheng
    • 1
  • Qiujun Qiu
    • 1
  • Chaoyang Lai
    • 1
  • Xinrong Liu
    • 1
  • Yihui Deng
    • 1
    Email author
  • Yanzhi Song
    • 1
    Email author
  1. 1.College of PharmacyShenyang Pharmaceutical UniversityShenyangChina

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