ABSTRACT
The potential for colloidal carriers to increase drug bioavailability has spurred a renewed interest in their uptake mechanisms and movement within cells. Solid lipid nanoparticles (SLN) were used as a carrier for a promising chemopreventive drug, resveratrol (RSV). The effects of SLN, empty or loaded with RSV (SLN-RSV), on the internalization, growth, morphology, metabolic activity and genetic material of keratinocytes were compared to those of RSV in solution. Fluorescence images clearly showed that SLN with a size below 180 nm move promptly through the cell membrane, distribute throughout the cytosol, move successively among different cellular levels and localize in the perinuclear region without inducing cytotoxicity. RSV solubility, stability and intracellular delivery were all increased by loading into SLN. The release profile of RSV showed a biphasic pattern, reflecting its distribution in SLN. RSV in solution was slightly cytotoxic. That was prevented by loading it into solid lipid nanoparticles, which preserved cell morphology. The cytostatic effect of SLN-RSV was much more expressed than that of RSV in solution. Delivery of RSV by SLN contributes to effectiveness of RSV on decreasing cell proliferation, with potential benefits for prevention of skin cancer.
Subject(s)
Drug Carriers/metabolism , Keratinocytes/metabolism , Lipids/chemistry , Nanoparticles/chemistry , Stilbenes/administration & dosage , Stilbenes/metabolism , Anticarcinogenic Agents/administration & dosage , Anticarcinogenic Agents/metabolism , Anticarcinogenic Agents/pharmacokinetics , Anticarcinogenic Agents/pharmacology , Biological Availability , Cell Cycle/drug effects , Cell Line, Transformed , Cell Nucleus/drug effects , Cell Proliferation/drug effects , Cell Shape/drug effects , Cell Size/drug effects , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/metabolism , Delayed-Action Preparations/pharmacology , Drug Carriers/chemistry , Drug Carriers/pharmacology , Humans , Hydrophobic and Hydrophilic Interactions , Intracellular Space/metabolism , Keratinocytes/cytology , Keratinocytes/drug effects , Lecithins/chemistry , Metabolism/drug effects , Microscopy, Fluorescence , Necrosis/chemically induced , Particle Size , Poloxamer/chemistry , Resveratrol , Static Electricity , Stilbenes/pharmacokinetics , Stilbenes/pharmacologyABSTRACT
The possibility of improving the efficacy of resveratrol, a polyphenol with strong antioxidant and free-radical scavenging properties, on cell proliferation and photoprotection by liposomal incorporation was investigated. Oligolamellar vesicles of different lipid compositions, loaded with resveratrol, were prepared and characterized by evaluating size, zeta potential, incorporation efficiency, electron microscopy and stability over 60 days. The effect of free and liposomal resveratrol on the viability of HEK 293 cells and their photoprotection after UV-B irradiation was assessed by the MTS method. Resveratrol decreased the cell viability at 100microM concentration, while at 10microM increased cell proliferation and also achieved the most effective photoprotection. Photomicrographs of the treated cells from inverted light and fluorescence microscopy demonstrated resveratrol effectiveness at 10microM, as well as its toxicity at higher concentrations, based on changes in cell shape, detachment and apoptotic features. Interestingly, liposomes prevented the cytotoxicity of resveratrol at high concentrations, even at 100microM, avoiding its immediate and massive intracellular distribution, and increased the ability of resveratrol to stimulate the proliferation of the cells and their ability to survive under stress conditions caused by UV-B light.