透明带3多肽-三甲基壳聚糖微球的制备及其在卵巢早衰中的应用

背景：透明带3多肽诱导口服耐受可预防及治疗自身免疫性卵巢早衰,但直接应用透明带3多肽治疗效果不十分理想,因此选择合适的药物载体系统成为进一步研究的基础。目的：制备透明带3多肽-三甲基壳聚糖微球,观察其在卵巢早衰中的作用。方法：采用离子交联法制备透明带3多肽-三甲基壳聚糖微球,观察微球形态,检测微球粒径、包封率、载药率及体外释放速度。分别以透明带3多肽-三甲基壳聚糖微球、磷酸盐缓冲液、透明带3多肽、三甲基壳聚糖灌胃治疗卵巢早衰小鼠。结果与结论：透明带3多肽-三甲基壳聚糖微球形态较规则,平均粒径280.5nm,包封率为69.20%,载药率为14.83%,随时间的延长,微球中透明带3多肽的体外释放率逐渐增加,无突释现象。透明带3多肽-三甲基壳聚糖微球组卵巢早衰小鼠外周血中抗透明带3多肽抗体阳性率明显低于其他3组（P〈0.05）,表明透明带3多肽-三甲基壳聚糖微球治疗可明显减低卵巢早衰小鼠血清中抗透明带3多肽抗体阳性率。

Preparation and application of zona pellucida 3 peptides-trimethyl chitosan microspheres in premature ovarian failure

BACKGROUND：Zona pellucida 3 peptide administered orally can prevent and treat the autoimmune premature ovarian failure.As the direct application is not very good,therefore,selecting the appropriate drug carrier system has become the basis for further research.OBJECTIVE：To prepare zona pellucida 3 peptides-trimethyl chitosan microspheres,and to study their application in premature ovarian failure METHODS：Zona pellucida 3 peptides-trimethyl chitosan microspheres were prepared by ionic cross-linking.Morphology of microspheres was examined by scanning electron microscope,and the microspheres size,encapsulation efficiency,drug loading rate and release rate were examined.The zona pellucida 3 peptides-trimethyl chitosan microspheres,PBS,zona pellucida 3 peptides and trimethyl chitosan microspheres were used respectively for the treatment of mice with premature ovarian failure.RESULTS AND CONCLUSION：The morphology of zona pellucida 3 peptides-trimethyl chitosan microspheres was regular.The average microsphere size was 280.5 nm,encapsulation efficiency was 69.20%,and drug loading rate was 14.83%.The in vitro release rate of zona pellucida 3 peptides-trimethyl chitosan microspheres was gradually increased with time passing without burst release phenomenon.The positive rate of anti-zona pellucida 3 peptides in the peripheral blood of premature ovarian failure mice in zona pellucida 3 peptides-trimethyl chitosan microspheres group was significantly lower than that in the other three groups （P 0.05）.It indicates that zona pellucida 3 peptides-trimethyl chitosan microspheres can significantly reduce the positive rate of anti-zona pellucida 3 peptides in the peripheral blood of premature ovarian failure mice.