受贻贝黏附蛋白主要成分的启发，开发其仿生黏附性材料在生物与医药领域具有重要的研究与应用价值。申请者前期研究发现，表面经该蛋白结构类似物聚多巴胺修饰的脂质纳米粒具有良好的皮内递药性能与皮肤相容性，但是其性质与递药作用间的关系、药物在皮肤各层组织中的分布特征及机制尚不明确。本项目拟在此基础上，选择特比萘芬与两性霉素B作为模型药物，通过改变多巴胺自聚-复合改性条件，构建具有不同涂层及粒子结构特征的仿生化纳米结构脂质载体；利用皮肤组织分布学研究，深入考察载体性质对不同层次皮内递药作用的影响；并结合对纳米粒与皮肤相互作用的研究，从角质细胞间脂质与皮肤附属器两种递药途径探索其作用机制与规律；此外，为提高其分散性以避免发生自聚现象，本项目构建一种温敏型离子液凝胶作为其基质，可在增强其稳定性的同时，进一步提高其体内递药能力。综上，本项目将为纳米粒系皮肤递药系统的设计、评价与机制研究提供有价值的借鉴与参考。

Inspired by the essential components of the mussel adhesive proteins, development of novel biomimetic adhesive materials has exhibited great prospect in the field of biology and medicine. In our previous investigation, it was found that the surface modified lipid nanoparticles with polydopamine, a structural analogue of mussel adhesive proteins, significantly promoted the intra-dermal drug delivery and exhibited excellent skin compatibility, while the underlying mechanisms, the drug distribution in different skin layers, as well as the relationship between their properties and the delivering effect have not been illustrated. Based on this research, terbinafine and amphotericin B would be selected as the model drug in the present study, and biomimetic nano-structure lipid carriers with different coatings and particle structures would be prepared by altering the conditions of self-polymerization-composite of dopamine. The influence of their structures and properties on the drug penetration into different skin layers would be studied in detail. For explaining their mechanisms of action, the interaction of nanoparticles with the skin, and the delivering effect via the intercellular route and follicle route would be also investigated. In addition, to enhance the dispersion of the bio-inspired nanoparticles and protect the system from self-aggregating, a temperature sensitive ionic liquid gel would be developed as the matrix of the above nano-carriers, which would also be helpful for its efficacy of the in vivo drug delivery. Above all, the study will provide some new ideas for the design, evaluation and mechanistic investigations on nanocarriers for skin drug delivery.