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Uptake and metabolism of novel biodegradable poly(glycerol-adipate) nanoparticles in DAOY monolayer

By Wei Meng, T.L. Parker, Paraskevi Kallinteri, D.A. Walker, Sean Higgins, Gillian A. Hutcheon and Martin C. Garnett

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

Topics: RC0254, RS
Publisher: Elsevier
Year: 2006
DOI identifier: 10.1016/j.jconrel.2006.09.014
OAI identifier: oai:kar.kent.ac.uk:18621
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