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Gate L , Vauthier C , Couvreur P , Tew KD , Tapiero H
Glutathione-loaded poly(isobutylcyanoacrylate) nanoparticles and liposomes: comparative effects in murine erythroleukaemia and macrophage- like cells
S T P Pharma Sciences. 2001 Sep-Oct;11(5) :355-361
AbstractGlutathione depletion has been related to various pathologies including cancer and neurological and cardiovascular diseases. Its bioavailability, is highly limited due to its poor cellular uptake and rapid turnover. In recent decades, various nanoparticular vectors have been developed to increase the bioavailability of therapeutic drugs. In the present work, glutathione (GSH) was loaded into poly(isobutylcyanoacrylates) (PiBCA), biodegradable nanoparticle vectors. These GSH-loaded particles were synthesized by dispersion polymerization in aqueous media. Although a considerable proportion of GSH (up to 50%) was loaded into these particles, no net increase in intracellular glutathione was observed in erythroleukaemia FLC or macrophage-like J774 cells unless previously treated with buthionine sulphoximine (BSO), a gamma-glutamyl cysteine synthetase inhibitor. Due to the non-efficacy of GSH-PiBCA particles, we incorporated GSH into liposomes [(soy phosphatidylcholine:cholesterol: dipalmitoyl phosphatidylglycerol (6:3: 1)] with an efficiency close to 25%. The glutathione content of BSO-depleted J774 cells could be restored when cells were exposed to GSH-loaded liposomes but increased beyond basal levels. These data suggest that GSH-loaded liposomes could be used to restore intracellular GSH in depleted cells, but did not influence GSH homeostasis under normal physiological conditions. The efficacy of this formulation tested in a clinical setting in patients with pathologies related to impaired cellular GSH levels has vet to be investigated.
NotesTapiero, H,Univ Paris Sud, Lab Pharmacol Cellulaire & Mol, Fac Pharm, CNRS,UMR 8612, 5 Rue Jean Baptiste Clement, F-92296 Chatenay Malabry, France Article English