Efficient delivery of paclitaxel into ASGPR over-expressed cancer cells using reversibly stabilized multifunctional pullulan nanoparticles

Liping Huang; Yutong Wang; Xiang Ling; Birendra Chaurasiya; Chen Yang; Yunai Du; Jiasheng Tu; Yerong Xiong; Chunmeng Sun

doi:10.1016/j.carbpol.2016.11.094

Efficient delivery of paclitaxel into ASGPR over-expressed cancer cells using reversibly stabilized multifunctional pullulan nanoparticles

Carbohydr Polym. 2017 Mar 1:159:178-187. doi: 10.1016/j.carbpol.2016.11.094. Epub 2016 Dec 2.

Authors

Liping Huang¹, Yutong Wang¹, Xiang Ling², Birendra Chaurasiya¹, Chen Yang¹, Yunai Du¹, Jiasheng Tu³, Yerong Xiong⁴, Chunmeng Sun⁵

Affiliations

¹ State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
² State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
³ State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: Jiashengtu@aliyun.com.
⁴ State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; The College of Science, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
⁵ State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: suncm_cpu@hotmail.com.

PMID: 28038747
DOI: 10.1016/j.carbpol.2016.11.094

Abstract

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 IC₅₀ 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.

Keywords: Disulfide bonds; Pullulan; Reducing sensitivity; Reversible core-crosslinking; Self-targeting.

MeSH terms

Asialoglycoprotein Receptor / metabolism*
Cell Line, Tumor
Drug Carriers / chemistry
Drug Delivery Systems*
Glucans / chemistry*
Humans
Nanoparticles / administration & dosage
Nanoparticles / chemistry*
Paclitaxel / administration & dosage*

Substances

Asialoglycoprotein Receptor
Drug Carriers
Glucans
pullulan
Paclitaxel