Neutrophil-Mediated Delivery of Dexamethasone Palmitate-Loaded Liposomes Decorated with a Sialic Acid Conjugate for Rheumatoid Arthritis Treatment
Neutrophil-Mediated Delivery of Dexamethasone Palmitate-Loaded Liposomes Decorated with a Sialic Acid Conjugate for Rheumatoid Arthritis Treatment
复制标题
中性粒细胞介导的唾液酸缀合物修饰的地塞米松棕榈酸酯脂质体的递送用于治疗类风湿关节炎
DOI：
10.1007/s11095-019-2609-4
复制
发表时间：
2019-07-01
影响因子：
3.7
通讯作者：
Song, Yanzhi
中科院分区：
文献类型：
--
作者：
Hu, Ling;Luo, Xiang;Song, Yanzhi
目的设计地塞米松棕榈酸酯（dexamethasone palmitate，DP）唾液酸修饰脂质体（sialic acid modified liposomes，SA-CH），以提高外周血中性粒细胞（peripheral blood neutrophil，PBNs）对类风湿关节炎（rheumatoid arthritis，RA）的治疗作用。评价了脂质体的理化性质和体外细胞毒性。采用流式细胞仪和激光共聚焦显微镜观察PBNs中脂质体的聚集情况。结果DP-CL和DP-SAL的平均粒径均小于200 nm，包封率均大于90%，脂质体具有良好的靶向性和抗炎作用。体内外实验表明，SA修饰的脂质体增强了DP在PBNs中的蓄积。此外，DP-SAL显示了更大程度的积累在关节和更强的抗炎作用方面的RA support. ConclusionsSA修饰的脂质体DP是一个有前途的候选人RA靶向治疗通过亲脂蛋白介导的药物输送系统。
PurposeThe 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).MethodsA 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.ResultsBoth DP-CL and DP-SAL existed an average size less than 200nm 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.ConclusionsSA-modified liposomal DP was a promising candidate for RA-targeting treatment through the neutrophil-mediated drug delivery system.