Self-assembled nanoparticles of reduction-sensitive poly (lactic-co-glycolic acid)-conjugated chondroitin sulfate A for doxorubicin delivery: preparation, characterization and evaluation

• Published in: Pharmaceutical development and technology 2019-07, Vol.24 (6), p.794-802
• Main Authors: Wang, Xu-Feng, Ren, Jin, He, Hai-Qing, Liang, Liang, Xie, Xin, Li, Zi-Xin, Zhao, Jian-Guo, Yu, Jing-Mou
• Format: Article
• Language: English
• Subjects: Chondroitin sulfate A; doxorubicin; drug delivery; nanoparticles; poly (lactic-co-glycolic acid)
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1080/10837450.2019.1599914

In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5 µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96 h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20 mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96 h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825 µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.