title: Efficient delivery of paclitaxel into ASGPR over-expressed cancer cells using reversibly stabilized multifunctional pullulan nanoparticles.
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 IC50at 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.
authors.affiliation: State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ling
authors.affiliation: State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Birendra
authors.initials: B
authors.lastname: Chaurasiya
authors.affiliation: State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Yunai
authors.initials: Y
authors.lastname: Du
authors.affiliation: State Key Laboratory of Nature Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: Jiashengtu@aliyun.com.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Tu
authors.affiliation: 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.
authors.forename: Yerong
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Sun
mesh_terms: D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005936:Glucans / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage*
chemical_list: D037263:Asialoglycoprotein Receptor; D004337:Drug Carriers; D005936:Glucans; C009109:pullulan; D017239:Paclitaxel
keywords: Disulfide bonds; Pullulan; Reducing sensitivity; Reversible core-crosslinking; Self-targeting