Improvements of cellular stress response on resveratrol in liposomes.
Resveratrol (RSV) has proven potential in prophylaxis and treatment of various disorders mediated by free radicals and oxidative stress. RSV solubility, stability, and cytotoxicity must be regulated for satisfactory bioavailability. Here, RSV was loaded into liposomes, characterized by PCS and TEM and evaluated on HEK293 cell line by metabolic activity assay, electron paramagnetic resonance, and fluorescence microscopy. RSV at 10 microM induced changes in cell metabolic activity and significantly improved antioxidative capacity. At 100 microM it showed concentration-dependent cytotoxicity. Oligolamellar liposomes with mean diameter 84 nm, polydispersity index 0.2, and zeta potential -40 mV showed high entrapment of RSV and rapid cellular internalization. Cell stress caused by UV-B irradiation diminished cell metabolic activity by 50%. RSV loaded into them showed no cytotoxicity at 100 microM and stimulated cellular metabolic and antioxidant activity levels to eliminate the harmful effect of the stress. Localization of RSV within liposomal bilayer is crucial for stimulation of cell-defense system, prevention of RSV cytotoxicity, and its long-term stability. In summary, evidence of different metabolic activity using free RSV and LIP-RSV is presented indicating that liposome-mediated uptake of RSV is more effective for improvement of the cell-stress response.
Kristl
Julijana
J
Department of Pharmacy, University of Ljubljana, Askerceva7, Ljubljana 1000, Slovenia. julijana.kristl@ffa.uni-lj.si
Teskac
Karmen
K
Caddeo
Carla
C
Abramović
Zrinka
Z
Sentjurc
Marjeta
M
D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001692:Biological Transport; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D010084:Oxidation-Reduction; D010316:Particle Size; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013312:Stress, Physiological / Q000187:drug effects* / Q000528:radiation effects; D013997:Time Factors; D014466:Ultraviolet Rays
D000975:Antioxidants; D008081:Liposomes; D013267:Stilbenes; D000077185:Resveratrol