他克莫司纳米晶合成及其表面人工泪液修饰研究

Synthesis of tacrolimus nanocrystals and artificial tears surface modification

目的制备集他克莫司（FK506）免疫抑制和人工泪液羧甲基纤维素钠（CMC）润滑双功能于一体的纳米药物,为临床治疗干眼症提供依据.方法首先采用超声法制备FK506纳米晶,进而利用层层自组装（LbL）技术将聚烯丙基胺盐酸盐（PAH）和CMC逐层交替沉积于FK506纳米晶表面,制备双功能纳米药物,并对其形态、粒径、表面电荷及组分等进行分析.结果FK506纳米晶粒径均一,FK506-（PAH/CMC）3近似球形,且表面凹凸不平.Zeta电位检测结果显示,LbL过程中随着包被层数的增加,Zeta电位呈正负交替变化,结合激光扫描共聚焦成像以及红外光谱等结果证实,PAH和CMC已成功修饰于FK506纳米晶表面.结论制备的FK506-（PAH/CMC）3纳米药物有望为联合治疗干眼症提供科学依据.

Objective To synthesize a dual-function nanodrug with immunosuppression of tacrolimus （FK506） and lubrication of artificial tear carboxymethylcellulose sodium （CMC）, and provide a basis for the clinical treatment of dry eye syndrome. Methods The FK506 nanocrystals were prepared by ultrasonic method, and polyallylamine hydrochloride （PAH） and CMC were deposited alternatively on the surface of FK506 nanocrystals using layer-by-layer （LbL） self-assembly technology to prepare the bifunctional nanodrug. The morphology, particle size, surface charge, and composition of the nanodrug were analyzed. Results The particle size of FK506 nanocrystals was uniform, and the FK506-（PAH/CMC）3 was approximately spherical with uneven surface. Zeta potential detection results showed that the charge changed alternatively with the increasing of layer number. The results of laser scanning confocal imaging and infrared spectroscopy showed that PAH and CMC were successfully modified on the surface of FK506 nanocrystals. Conclusion The prepared FK506-（PAH/CMC）3 nanodrug is expected to provide a scientific basis for the combined treatment of dry eye.