title: Enhanced cellular uptake and anti-proliferating effect of chitosan hydrochlorides modified genistein loaded NLC on human lens epithelial cells.
abstract: This study was attempted to increase the cellular uptake of developed genistein loaded nanostructured lipid carriers (NLC) into human lens epithelial (HLE) cells by chitosan hydrochlorides coatings when applied in post lens capsule (PCO) treatment, and to provide further understanding of the uptake and anti-proliferation mechanisms inside. NLCs were produced using melt-emulsification method and were subsequently coated with chitosan hydrochlorides by adsorption. The uptake of various particle sizes were evaluated and visualized by confocal laser scanning microscopy (CLSM), showing a size-dependent manner. The uptake of NLC was proved to be endocytosed in an energy dependent and clathrin-mediated endocytosis to HLE cells by the decrease in uptake at lower temperature, when pre-saturated by blank NLC and in the presence of NaN3 and sucrose. CH coating improved the uptake percentage of NLC irrespective of the particle size, without influencing the uptake mechanism. Cell apoptosis was tested using PI and Annexin V-FITC/PI staining, followed by flow cytometer analysis. Higher anti-proliferation effect was observed for CH-NLC in inhibiting the growth of HLE cells by causing more apoptosis. Results above indicate that GEN-NLC surface modified by chitosan hydrochlorides could enhance the trans-cellular performance and anti-proliferating effect as PCO therapy.
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Wenji
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of ophthalmology, Affiliated Fourth Hospital of China Medical University, Shenyang 110005, China.
authors.forename: Jinlu
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of ophthalmology, Affiliated Fourth Hospital of China Medical University, Shenyang 110005, China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of ophthalmology, Affiliated Fourth Hospital of China Medical University, Shenyang 110005, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Kong
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: pppwwwsss@163.com.
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D019833:Genistein / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D008055:Lipids; D047428:Protein Kinase Inhibitors; D048271:Chitosan; D019833:Genistein; D011505:Protein-Tyrosine Kinases
keywords: Apoptosis; Cellular uptake; Chitosan hydrochloride; Genistein; NLC