壳聚糖
胶束
氧化还原
Zeta电位
化学
药物输送
两亲性
纳米技术
生物物理学
材料科学
纳米颗粒
生物化学
共聚物
有机化学
生物
水溶液
聚合物
作者
Hamed Vakilzadeh,Jaleh Varshosaz,Mohammad Dinari,Mina Mirian,Valiollah Hajhashemi,Nahal Shammaeizadeh,Hamid Mirmohammad Sadeghi
标识
DOI:10.1016/j.ijbiomac.2022.12.111
摘要
Dasatinib (DAS) exhibits anti-inflammatory effects by retrieving the balance between inflammatory and anti-inflammatory cytokines secreted by macrophages. The aim of this study was the development of redox-responsive micelles with the potential of passive targeting and on-demand drug release for DAS delivery to macrophages. For this purpose, two molecular weights of chitosan (CHIT) were conjugated to DAS at different molar ratios using 3,3′-dithiodipropionic anhydride (DTDPA) as disulfide bond containing linker to synthesize a series of CHIT-S-S-DAS amphiphilic conjugates. Micelles obtained by the sonication method had particle sizes of 129.3–172.2 nm, zeta potentials of +17.5 to +20.9 mV, drug contents of 0.90–7.20 %, CMC values of 35.3–96.6 μg/ml, and exhibited redox-responsive in vitro drug release. Optimized micelles were non-toxic and dramatically more efficient than non-redox responsive micelles in reducing TNF-α and IL-6 and increasing IL-10 secretion from LPS-stimulated RAW264.7 cells. Furthermore, the redox-responsive micelles were able to reduce the mice paw edema, reduce the plasma levels of pro-inflammatory cytokines and increase plasma level of IL-10, considerably more than free DAS and non-redox responsive micelles in carrageenan-induced mice paw edema model of inflammation.
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