Core-crosslinked pullulan nanoparticles (Pull-LA-CLNPs) were synthesized by the reduction-sensitive strategy for paclitaxel (PTX) delivery. Pull-LA-CLNPs showed high stability against extensive dilution, high salt concentration and organic solvent. In vitro drug release study showed that PTX release from Pull-LA-NPs at pH 7.4 and 5.4 was significantly influenced by addition of DTT. In cytotoxicity assay, PTX loaded Pull-LA-CLNPs showed a low IC at 0.51μg/mL. Asialoglycoprotein receptor (ASGPR) competitive inhibition and intracellular distribution studies performed by flow cytometer, fluorescence microscope and confocal laser scanning microscopy (CLSM) showed that Pull-LA-NPs could be efficiently taken up by the cells via ASGPR-mediated endocytosis and mainly distributed in cytoplasm. From in vivo pharmacokinetics study, Pull-LA-CLNPs displayed the longest systemic retention time and slowest plasma elimination rate in comparison with Taxol and Pull-LA-NCLNPs. In conclusion, Pull-LA-CLNPs is a promisingly safe, biodegradable and cell-specific nano-carrier to deliver lipophilic anticancer drugs.
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| http://dx.doi.org/10.1016/j.carbpol.2016.11.094 | DOI Listing |
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