鼠李糖类似物介导的脂质体递药系统及其靶向抗胰腺癌的研究

Rhamnose-analogues mediated liposomal drug delivery system for pancreatic cancer target therapy

本文初步探究了鼠李糖类似物作为靶向配体构建递药系统,实现胰腺癌主动靶向治疗的可行性。采用薄膜水化法成功制备了鼠李糖脂脂质体,并对其理化性质、体外释放特性、体内外靶向性及体外药效学进行了初步评价。鼠李糖脂脂质体在体内外均能表现出针对人胰腺癌(BxPC-3)细胞的良好靶向性,且具有更强的抗肿瘤效果。基于此,进一步以鼠李糖脂天然结构类似物重楼皂苷VII(Polyphyllin VII,PPVII)为靶向材料及活性成分,探索重楼皂苷VII脂质体(Polyphyllin VII modified liposomes,PPVII-Lip)对BxPC-3细胞的靶向性及抗肿瘤活性研究。结果表明,PPVII-Lip粒径均一,在体内对BxPC-3实体瘤有较强的靶向能力,能够提高药物在胰腺癌肿瘤部位选择性富集。在体内、外药效评价中,相比胰腺癌一线化疗药物吉西他滨,PPVII-Lip对胰腺癌细胞也表现出更强的抑制效果。综上所述,该靶向递药策略有望为靶向治疗胰腺癌的药物递送研究提供有益的思路。本研究体内动物实验得到了西南大学动物伦理委员会的批准(批准号:IACUC-20210130-2)。

In this study,we have firstly investigated the feasibility of rhamnolipids as targeting ligands to develop drug delivery systems for active targeting of pancreatic cancer.Rhamnolipid-modified liposomes(RhaL-Lip)were prepared by a thin film hydration method,and were evaluated preliminarily for RhaL-Lip physicochemical properties,in vitro release characteristics,ex/in vivo targeting,and in vitro pharmacodynamics.RhaL-Lip exhibited excellent targeting ability of human pancreatic cancer(BxPC-3)cells and enhanced anti-tumor effects.On this basis,the natural structural analogue of rhamnolipid,PolyphyllinVII(PPVII),as the targeting material and active ingredient,we explored the targeting and anti-tumor activity of PolyphyllinVIImodified liposomes(PPVII-Lip).The results showed that PPVII-Lip has a homogeneous particle size and has a more robust targeting ability for solid tumor in vivo,which can achieve more enrichment at the tumor site.Compared with gemcitabine,the first-line chemotherapy drug for pancreatic cancer,PPVII-Lip showed a stronger inhibitory effect.In conclusion,this targeted drug delivery strategy is expected to provide beneficial ideas for drug delivery studies in targeted therapy for pancreatic cancer.Animal experiments were conducted with approval from the Animal Ethics Committee of southwest university(approval number:IACUC-20210130-2).