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

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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.

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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

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Author notes

  1. Ling Hu and Xiang Luo contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, China

    Songlei Zhou, Jingyang Zhu, Mingyue Xiao, Cong Li, Huangliang Zheng, Qiujun Qiu, Chaoyang Lai, Xinrong Liu, Yihui Deng & Yanzhi Song

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  1. Ling Hu
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  2. Xiang Luo
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  3. Songlei Zhou
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Correspondence to Yihui Deng or Yanzhi Song.

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Hu, L., Luo, X., Zhou, S. et al. Neutrophil-Mediated Delivery of Dexamethasone Palmitate-Loaded Liposomes Decorated with a Sialic Acid Conjugate for Rheumatoid Arthritis Treatment. Pharm Res 36, 97 (2019). https://doi.org/10.1007/s11095-019-2609-4

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