title: Uptake and metabolism of novel biodegradable poly (glycerol-adipate) nanoparticles in DAOY monolayer.
abstract: A useful route for the development of antitumour therapies is by creating improved methods for delivering therapeutic agents to tumour cells or subcellular compartments and increasing retention of drugs within target cells. In this study, we have characterized nanoparticle (NP) uptake and metabolism by DAOY cells, a human medulloblastoma cell line. NPs were formed from a novel polymer, poly (glycerol-adipate) (PGA), containing Rhodamine B Isothiocyanate (RBITC) as a fluorescent marker. It was observed that the cellular uptake of NPs depends on the incubation time and the concentration of NPs in the culture medium. The studies of retention and metabolism of NPs within cells indicated that 1) faster degradation of NPs within cells compared with that in cell culture medium in vitro; 2) a small fraction of NPs were recycled back to the outside of cell, whereas most NPs entered endosomes and lysosomes; and 3) recycled NPs were re-taken up in the following 2 h incubation time. These studies thus suggested that PGA NPs could be used for localising therapeutic agents into cells, and could provide prolonged drug effects because of their long sustained release in physiological conditions and their rapid release when taken up into cells.
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: W
authors.initials: W
authors.lastname: Meng
authors.forename: T L
authors.initials: TL
authors.lastname: Parker
authors.forename: P
authors.initials: P
authors.lastname: Kallinteri
authors.forename: D A
authors.initials: DA
authors.lastname: Walker
authors.forename: S
authors.initials: S
authors.lastname: Higgins
authors.forename: G A
authors.initials: GA
authors.lastname: Hutcheon
authors.forename: M C
authors.initials: MC
authors.lastname: Garnett
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000378:metabolism*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters / Q000378:metabolism*; D012995:Solubility; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D011091:Polyesters; C517626:poly(glycerol-adipate)