RRC ID 19274
Author Tahara K, Sakai T, Yamamoto H, Takeuchi H, Hirashima N, Kawashima Y.
Title Improved cellular uptake of chitosan-modified PLGA nanospheres by A549 cells.
Journal Int J Pharm
Abstract The authors have previously developed poly(DL-lactic-co-glycolic acid) (PLGA) nanospheres (NSs) as a nanoparticulate drug carrier for pulmonary administration. The present study demonstrates that chitosan (CS)-modified PLGA NSs (CS-PLGA NSs) are preferentially taken up by human lung adenocarcinoma cells (A549). PLGA NSs prepared using a water-oil-water emulsion solvent evaporation method were surface-modified by adsorption of CS. The physicochemical parameters of PLGA NS, including average size and surface charge, were measured to identify which parameter influenced cellular uptake of PLGA NS. Uptake was confirmed using fluorescence spectrophotometry and was visualized in A549 cells with confocal laser scanning microscopy (CLSM). The cytotoxicities of non- and CS-PLGA NS systems were compared in vitro by MTS assay. Cellular uptake of PLGA NS increased with decreasing diameter to the submicron level and with CS-mediated surface modification. Cellular uptake of PLGA NS was energy dependent, as shown by a reduction in uptake at lower incubation temperatures and in hypertonic growth medium used as an inhibitor of clathrin-coated pit endocytosis. CS-PLGA NSs were taken up by A549 cells in an energy-dependent manner, suggesting a clathrin-mediated endocytic process. CS-PLGA NS demonstrated low cytotoxicity, similar to non-PLGA NS.
Volume 382(1-2)
Pages 198-204
Published 2009-12-1
DOI 10.1016/j.ijpharm.2009.07.023
PII S0378-5173(09)00495-5
PMID 19646519
MeSH Adenocarcinoma / metabolism* Biological Transport, Active Cell Line, Tumor Cell Survival / drug effects Chemistry, Pharmaceutical Chitosan / chemistry Chitosan / metabolism* Chitosan / toxicity Clathrin / metabolism Coated Pits, Cell-Membrane / metabolism Dose-Response Relationship, Drug Drug Carriers* Endocytosis Humans Hypertonic Solutions Kinetics Lactic Acid / chemistry Lactic Acid / metabolism* Lactic Acid / toxicity Lung Neoplasms / metabolism* Microscopy, Confocal Nanospheres* Particle Size Polyglycolic Acid / chemistry Polyglycolic Acid / metabolism* Polyglycolic Acid / toxicity Polylactic Acid-Polyglycolic Acid Copolymer Spectrometry, Fluorescence Surface Properties Technology, Pharmaceutical / methods Temperature
IF 4.213
Times Cited 96
Human and Animal Cells A549 (RCB0098)