多肽类药物载体纳米羟基磷灰石的合成及应用研究

Study on Application and Synthesis of Polypeptide Drug Carrier Nano-Hydroxyapatite

摘要: 以镁离子为成核诱导剂，采用水热法制备出颗粒均匀的近似球形的纳米羟基磷灰石(nHAP)，并利用FTIR、SEM、TEM等手段对其进行表征。将nHAP作为多肽类药物载体，重点探讨了时间、温度、pH等条件对nHAP负载胰岛素的影响，制备负载胰岛素的纳米羟基磷灰石(INS-nHAP)，并评价其释药性能。结果显示：当胰岛素浓度为1 mg/mL，吸附3 h，吸附体系温度为30℃，且pH = 3时，INS-nHAP中有效含量3.98%wt，包封率高达92.66%wt；前6 h内对应体外药物释放呈零级释放特征，累积释放率达到72.71%wt，约为55.58个单位的INS，接近人正常生理条件下的胰岛素分泌速率；以INS-HAP基础制备的海藻多糖凝胶贴具有明显的糖尿病创口愈合促进作用。

Abstract: In this work, nano-hydroxyapatite (nHAP) particles, with uniform particle size and approximate spherical shape, were prepared by hydrothermal method using magnesium ion as nucleation in-ducer. nHAP was characterized by FTIR, SEM and TEM etc. The effects of insulin loading, such as loading time, loading temperature, pH of the solution for loading, and so on, were discussed. Insulin loaded nano-hydroxyapatite (INS-nHAP) was prepared. At the same time, release properties of INS-nHAP were evaluated. The results showed that the effective content of INS-nHAP was 3.98%wt, and the encapsulation efficiency was 92.66%wt when the concentration of insulin was used in 1 mg/mL, with pH = 3, 30˚C of the adsorption system temperature and 3 hours of the adsorption time. The cumulative release rate of INS-nHAP was 72.71%wt during the first six hours, which was about 55.58 units of INS, and was closed to the rate of insulin secretion under normal physiological conditions. The gel based on alginate polysaccharide and INS-HAP has obvious promotion effect on diabetic wound healing.