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Smart Redox-Sensitive Micelles Based on Chitosan for Dasatinib Delivery in Suppressing Inflammatory Diseases Publisher Pubmed



Vakilzadeh H1 ; Varshosaz J1 ; Dinari M2 ; Mirian M3 ; Hajhashemi V4 ; Shamaeizadeh N1 ; Sadeghi HMM3
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Authors Affiliations
  1. 1. Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Chemistry, Isfahan University of Technology, Isfahan, Iran
  3. 3. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Pharmacology, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan, Iran

Source: International Journal of Biological Macromolecules Published:2023


Abstract

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. © 2022
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