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目的制备具有良好靶向性的硼脂质体,为硼中子俘获治疗的研究与应用建立一个有效的靶向给药途径。方法采用新型的主动载药方法pH梯度法制备硼脂质体,分析不同药脂比例对包封率的影响,优化Trastuzumab连接到DSPEPEGNHS分子微团的时间因素,采用微团转移法将TrastuzumabPEGDSPE掺入预先制备的硼脂质体,比较不同时间和温度对掺入量的影响,测试脂质体的稳定性、温度对Trastuzumab与受体结合能力的影响以及硼脂质体的受体靶向特异性。结果制备的硼脂质体大小均匀,直径约为100nm,圆形小囊状,药物包封率高。Trastuzumab与DSPEPEGNHS室温下孵育1h可达到足够高的连接率。60℃的水浴中作用4h,90%的TrastuzumabPEGDSPE掺入了脂质体脂膜。脂质体稳定,37℃保存2周仍有95%的抗体与脂质体相连。实验所用温度对Trastuzumab与HER2结合的能力影响不大。制备的硼脂质体与HER2受体的结合能被浓度不断增高的Trastuzumab所置换。结论本法制备的硼脂质体大小均匀,外观圆整,药物包封率高,有良好稳定性。实验过程对抗体特性无明显影响,硼脂质体具备与HER2受体特异性结合的能力。
OBJECTIVE: To prepare boron liposomes with good targeting ability and to establish an effective targeted drug delivery route for the research and application of boron neutron capture therapy. Methods Borosomal liposomes were prepared by a novel active drug loading method and pH gradient method. The effects of different drug-lipid ratios on the entrapment efficiency were analyzed. The time factor of Trastuzumab connecting to DSPEPEGNHS molecular micelles was optimized. Trastuzumab PEGDSPE was incorporated by micellar transfer Pre-prepared boron liposomes were compared in different time and temperature on the amount of incorporation, the stability of the tested liposomes, the effect of temperature on the binding ability of Trastuzumab to the receptor, and the targeting specificity of boron liposomes . Results The prepared liposomes were uniform in size, about 100 nm in diameter and small in size. The drug encapsulation efficiency was high. Trastuzumab and DSPEPEGNHS incubated for 1 h at room temperature to achieve a high enough connectivity. 60 ℃ water bath for 4h, 90% of TrastuzumabPEGDSPE incorporation of liposomes. Liposomes are stable and 95% of the antibodies still remain attached to the liposomes at 37 ° C for 2 weeks. The experimental temperature had little effect on the ability of Trastuzumab to bind to HER2. The binding of the prepared boron liposomes to the HER2 receptor can be displaced by increasing concentrations of Trastuzumab. Conclusion Borodiposomes prepared by this method are uniform in size and round in appearance with high encapsulation efficiency and good stability. Experimental process on the characteristics of the antibody had no significant effect, boron liposomes with HER2 receptor with specific binding capacity.