| Quercetin (QT,3,3',4',5,7-pentahydroxyflavone) is a natural flavonoid, which is known to have a variety of biological activities and pharmacological actions, such as anticancer, antioxidation, anti-inflammation, decreasing blood lipid, dilating coronary arteries, anti-platelet aggregation, antianemic action, anti-anaphylaxis. Recently, quercetin as free radical scavenger has been attracted more and more attentions. However, quercetin with low solubility and light and temperature sensitivity, can be absorbed little in vivo, which greatly limit its clinical use.Nanostructured lipid carriers (NLC) are novel lipid-based nanoparticles which are composed of liquid and solid lipids. The addition of liquid lipid can disturb the highly regular lattice structure, incrase the ratio of irregular lattice structure in nanoparticles, and further increase the space for accommodating drugs. The advantages for NLC applying topically are as follows:the biocompatible NLC does not cause skin irritation; the effect of occulusive caused by application of the nano-sized particles on the skin can increase the drug permeation; the components of NLC such as egg phosphatidylcholine can be acted as permeation enhancers; NLC can increase the stability of embedded durgs and improve the behavior of drug release.Quercetin-loaded nanostructured lipid carriers (QT-NLC) were prepared using the method of emulsification and low-temperature solidification. Based on the single factor experiment, the amount of drug, the concentration of surfactant, the amount of cosurfactant, the ratio of glyceryl monostearate to stearic acid, the amount of liquid lipid, emulsifying temperature were proved to have great effects on the properties of QT-NLC. The uniform experimental design was applied to optimize the formulation based on entrapment efficiency and drug loading of QT-NLC. The average entrapment efficiency and drug loading of the optimized formulation were 89.95% and 3.05% respcetively. Under the transmission electron microscope, these nanoparticles were spherically shaped, and the average particle size was 264.5nm. The zeta potential was -20.10mV and pH value was 4.65. The behavior of drug release from QT-NLC was investigated using the method of dialysis. The results showed that the drug release of QT-NLC in vitro fit double phase kinetics model well. The equation for drug release of QT-NLC in vitro was as follows:100-Qn =100.786e0.0775t+53.293e0.0227t (rα=0.9939, rβ=0.9956). The results of stability experiment showed that QT-NLC should be stored under the condition of low temperature and away from light.Franz diffusion cells were used to study the permeation behaviour of QT-NLC in vitro. The results showed that the cumulative drug amount penetrating through the excised mouse skin at 12h after administration of QT-propylene glycol and QT-NLC were 9.00±1.19 and 31.89±3.15μg·cm-2, and the steady-state permeation rates were 1.153±0.11μg·cm-2·h-1 and 3.503±0.27μg·cm-2·h-1, respectively, which exhibited that QT-NLC could significantly promote the permeation of drug to skin. The amount of drug permeating into epidermis and dermis from QT-NLC were respectively 1.52 times and 3.03 times that from QT-propylene glycol at 12h after topical administration in mice. The results showed that QT-NLC could obviously increase the amount of drug retention in epidermis and dermis, and further enhance the effect of antioxidation and anti-inflammation exerted by QT.The results of pathological sections revealed that the skins treated by QT-NLC showed scattered and loose stratum corneum. Meanwhile, the stratum corneum appeared swollen and overall thickness of the skin obviously increased. Moreover, cell conjuction was broken and cell gaps increased. In a conclusion, QT-NLC could weaken the barrier function of stratum corneum and promote drug permeation. |
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