Self-assembled nanoparticles of reduction-sensitive poly (lactic-co-glycolic acid)-conjugated chondroitin sulfate A for doxorubicin delivery: preparation,characterization and evaluation |
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Authors: | Xu-Feng Wang Hai-Qing He Liang Liang Xin Xie Zi-Xin Li |
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Affiliation: | 1. School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, China;2. Analytical and Testing Center, Jiujiang University, Jiujiang, China;3. College of Basic Medical Science, Jiujiang University, Jiujiang, China |
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Abstract: | 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. |
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Keywords: | Chondroitin sulfate A poly (lactic-co-glycolic acid) nanoparticles drug delivery doxorubicin |
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