和厚朴酚与siRNA共递送的阳离子脂质体研究

Cationic Liposomes for the Co-delivery of siRNA and Honokiol

目的利用聚乙二醇(PEG)修饰的阳离子脂质体实现和厚朴酚与siRNA的共递送以改善肿瘤治疗效应。方法利用薄膜分散法制备聚乙二醇修饰的阳离子脂质体,通过疏水作用包载和厚朴酚以及静电吸附作用包载siRNA的方式,构建共递送和厚朴酚与siRNA的阳离子脂质体。通过粒径、电位、包封率、血清稳定性等方法考察脂质体的制剂学性质,并考察了制剂的细胞摄取与胞内分布、溶酶体逃逸能力以及肿瘤细胞生长抑制效应。结果所制备的各组载和厚朴酚脂质体的平均粒径均在100 nm以内,均具有较高的药物包封率。优选的共递送脂质体制剂(N/P=5)具有较好的血液稳定性,可获得较高的细胞摄取和较好的胞内溶酶体逃逸能力;和厚朴酚与siRNA的协同效应具有较好的抑制肿瘤细胞生长效果。结论采用聚乙二醇修饰的阳离子脂质体可以实现和厚朴酚和siRNA的共递送并将可能有利于体内肿瘤治疗。

OBJECTIVE To develop a polyethylene glycol （PEG） modified cationic liposomes for the co-delivery of siRNA and honokiol to improve tumor therapy. METHODS The PEG-modified cationic liposomes were prepared by thin film hydration method. Honokiol was loaded in the liposomes with hydrophobic interaction and siRNA was loaded with electrostatic interaction. The optimal formulation was screened according to size, Zeta potential, entrapment efficiency and serum stability. The liposomes were characterized with cellular uptake and intracellular localization of siRNA. The pharmaeodynamic effect of honokiol-loaded liposomes （LH） and honokiol-siRNA-loaded liposomes （LH-siRNA） were verified by inhibition of cancer cell growth. RESULTS All the honokiol-loaded liposomes had an average particel size of about 100 nm with high drug entrapment efficiency. The optimal liposome formulation （ N/P ratio of 5 ） exhibited the best cellular uptake. The results of pH-dependent hemolysis and intracellular localization suggested that the LH-siRNA had good ability of endosomal escape. In vitro cell growth experiments showed that both LH and LH-siRNA had good inhibition action on tumor cell growth based on the effects of honokiol and siRNA. CONCLUSION The PEG-modified cationic liposomes can be a potential carrier for co-delivery of siRNA and honokiol to tumors.