| Quercetin (QT) is a natural flavonoid, which is known to have a variety of biological activities and pharmacological actions such as anti-inflammatory, anti-allergy, antioxidation, anticancer, anti-HIV, anti-arrhythmic. Meanwhile, QT has slight side effects, and will not induce teratogenic, carcinogenic and lethal injury to body. All these advantages make QT an ideal candidate for clinical research. However, the low solubility, and temperature and light sensitivity of QT greatly limit its clinical use.Lecithin/chitosan nanoparticles (L/CS NPs) is a novel colloidal nano-carrier system which are composed of two natural polymers, negatively charged lecithin and positively charged chitosan. The two polymers can form round-shaped nanoparticles by electrostatic interaction with small size and large specific surface area. The outer shell of L/CS NPs is composed of chitosan, and it is bioadhesive, which makes L/CS NPs to form an adhesive film on skin. Additionally, the chitosan outer shell is positive charged, which can closely contact with negatively charged surface of the skin by electrostatic interaction, and thus improving the degree of hydration of the stratum corneum, reducing the barrier function, and promote the infiltration of drugs into the skin.Quercetin-loaded lecithin/chitosan nanoparticles (QT-L/CS NPs) were prepared with the method of organic solvent injection. The single factor experiment was applied to optimize the formulation. Morphology, encapsulation efficiency and drug loading were as evaluation indexs to determine the optimized formulation. Under the transmission electron microscope, these nanoparticles were spherically shaped, and the average particle size, the zeta potential and pH value were95.3nm,+10.85mV and4.5, respectively. And the average entrapment efficiency and drug loading of the optimized formulation were48.47%and2.45%respcetively. The results of stability experiment showed that QT-L/CS NPs should be stored under the condition of low temperature and away from light.The permeation behaviour of QT-L/CS NPs in vitro showed that QT was rarely penetrated through excised mouse skin and there was nearly no QT in the receptor medium at12h after administration. But the cumulative drug amount in epidermis and dermis were9.00μg·cm-2and3.31μg·cm-2, which were1.45and1.32times that of control group (QT-propylene glycol). The results of in vivo permeation study showed that the amount of drug permeating into epidermis and dermis from QT-L/CS NPs were respectively2.3times and1.2times that from control group (QT-propylene glycol) at12h after topical administration in mice. The results demonstrated that QT-L/CS NPs could obviously increase the amount of drug retention in epidermis and dermis, especially in epidermis, 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-L/CS NPs 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-L/CS NPs could weaken the barrier function of stratum corneum and promote drug permeation.The anti-inflammatory study showed that the xylene-induced acute skin inflammation on mouse ear skin can be greatly inhibited and mitigated by QT-L/CS NPs, and blank L/CS NPs themselves have had no irritation on mouse ear skin. So QT-L/CS NPs is safe and reliable delivery system... |
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