普鲁兰基肿瘤靶向性纳米粒子的制备、稳定性和体外释放

Tumor-targeted nanoparticles derived from pullulan acetate conjugate:Preparation,stability and release in vitro

背景:普鲁兰多糖以其独特的优点在纳米递药系统领域受到越来越多的关注,但是,以普鲁兰多糖为材料进行改性制备的肿瘤靶向的纳米药物载体仍有待进一步研究与开发。目的:观察纳米粒子和载药纳米粒子的体外稳定性及所包载药物的释放特征,初步评价其作为纳米药物载体的潜力。方法:应用透析法制备乙酰普鲁兰叶酸偶合体纳米粒子,以表阿霉素为模型药物,制备乙酰普鲁兰叶酸偶合体/表阿霉素载药纳米粒子(FPA/EPI),应用储存法考察其稳定性,应用透析袋法观测体外释放特征。结果与结论:乙酰普鲁兰叶酸偶合体纳米粒子和FPA/EPI的粒径分别为(204.2±10.9)nm和(273.4±11.0)nm,在蒸馏水和体积分数10%胎牛血清中表面电位均较低,乙酰普鲁兰叶酸偶合体纳米粒子在水溶液中粒径1年内未见显著改变。载药纳米粒子对所包载的药物表阿霉素进行很好地释放,pH5.0磷酸盐缓冲液中释放速度明显高于pH7.4;乙酰普鲁兰叶酸偶合体纳米粒子和FPA/EPI制备容易,稳定性好,初步说明了两种粒子可望成为新型肿瘤靶向药物递药系统。

BACKGROUND：Pullulan due to its many unique characteristics have received more and more attention in the field of drug delivery systems.But,the tumor targeted nano-drug carriers based on pullulan needed to be further studied and developed.OBJECTIVE：To observe the stability and drug release in vitro of nano-drug carriers and to preliminarily evaluate the potential of folate conjugated pullulan acetate（FPA） as a nano-drug carrier.METHODS：Folate was coupled to pullulan acetate（PA）.FPA nanoparticles（FPAN） and epirubicin-loaded FPA nanoparticles（FPA/EPI） were prepared by dialysis method.The storage stability of FPAN and FPA/EPI was observed by storage method,and the in-vitro release characteristics were studied by dialysis bag method.RESULTS AND CONCLUSION：FPAN and FPA/EPI had the nearly spherical shape with a size range of（204.2±10.9） nm and（273.4±11.0） nm,respectively,and they had low ζ potentials both in water and in 10% fetal bovine serum.FPAN maintained stable for at least 1 year.The drug encapsulated in FPAN was released more quickly in pH 5.0 PBS than in pH 7.4.It is concluded that the FPA nano-drug carrier is easy to prepare and has good stability.FPA and FPA/EPI nanoparticles have the potential to be new tumor-targeted nano-drug delivery systems.