Optimized the gene and drug delivery using liposomes based on the controlled liposomal surface property

脂质体是药物和基因的载体，但开发新型高效、细胞选择性的载体系统对各类药物的临床应用至关重要。在本研究中，我们评估了新的表面修饰的脂质体的目的，开发先进的脂质体，具有细胞选择性的性质或控制与内源性成分的相互作用。在本研究中，我们合成了新型的半乳糖基化和甘露糖基化胆固醇衍生物，分别用于肝实质细胞和非实质细胞的药物和基因递送。这些衍生物具有双功能特性，即胆固醇用于将糖部分固定在脂质体表面上，糖残基用于细胞表面受体。体外研究表明，糖基化脂质体能有效地吸收受体介导的内吞作用。静脉给药后，糖基化脂质体被表达受体的细胞有效摄取。我们还制备了糖基化阳离子脂质体/质粒DNA复合物，用于肝细胞选择性基因递送。受体介导的基因递送系统能够在体内将外源DNA引入特定细胞类型。然而，我们已经证实，不仅是性质的配体接枝到载体，而且脂质组成和物理化学性质的复合物需要进行优化，有效的细胞选择性靶向质粒DNA。总之，我们研制了新型的细胞选择性药物和基因载体，可以控制药物和基因的生物分布。

Although liposomes are focused on the drug and gene carriers, it is essential to develop the novel effective and cell-selective carrier systems for the clinical application of the various types of drugs. In the present study, we evaluated the novel surface modified liposomes for the purpose of development the advanced liposomes, which possessed the cell-selective properties or controlled interaction with endogenous component. In the present study, we synthesized novel galactosylated and mannosylated cholesterol derivatives for drug and gene delivery to liver parenchymal cell and non-parenchymal cell, respectively. These derivatives possess bi-functional properties i.e. cholesterol for the fix the sugar moiety on liposomal surface and a sugar residue for the cell surface receptors. In vitro study demonstrated that the glycosylated liposomes were efficiently taken up the receptor-mediated endocytosis. After intravenous administration, glycosylated liposomes were effectively taken up by the cells, which expressed the receptor. We also prepared the glycosylated cationic liposomes/plasmid DNA complexes for the liver cell-selective gene delivery. Receptor-mediated gene delivery systems are able to introduce foreign DNA into specific cell types in vivo. However, we have confirmed that not only the nature of the ligands grafted to carriers but also the lipid composition and physicochemical properties of the complexes need to be optimized for effective cell-selective targeting of plasmid DNA. In conclusion, we developed the novel cell-selective drug and gene carriers, which can be controlled the biodistribution of drug and gene.