载长春瑞滨红细胞载药体系的建立及其体外评价

Establishment of drug delivery systems of vinorelbine-loaded erythrocytes and the in-vitro evaluation

目的建立载长春瑞滨红细胞载药体系并评价其功能。方法利用改良低渗预膨胀法制备载长春瑞滨红细胞载药体系,采用紫外分光光度计测定长春瑞滨载药量和包载率,并对其体外贮存、释药情况进行评估。利用噻唑蓝(MTT)法评价载长春瑞滨红细胞的细胞增殖抑制作用。结果载长春瑞滨红细胞包载率为70.92%,在体外能稳定贮存5 d,包载过程中红细胞形态、性质无明显变化,载体红细胞对包载的长春瑞滨可以稳定释放,48 h释放率接近100%。载药红细胞对人肺腺癌细胞株A549作用48 h后,当长春瑞滨浓度为0.0125、0.025 mg/ml时,载长春瑞滨红细胞组的细胞增殖抑制率高于裸药长春瑞滨组(P﹤0.05),且产生相同抑制率时,载长春瑞滨红细胞组所需要的长春瑞滨浓度低于裸药长春瑞滨组。结论本研究建立的载长春瑞滨红细胞载药体系性质稳定,具有缓释作用,且在一定药物浓度下能提高疗效。

Objective To establish the drug delivery system of vinorelbine-loaded erythrocytes and evaluate the appli-cability in vitro. Methods Establishing carrier erythrocytes using a modified hypotonic preswelling technique. The drug loading, encapsulation efficiency of vinorelbine and release in vitro were detected by ultraviolet spectrophotometer. Cell proliferation inhibition was measured by MTT to compare the cytotoxicity of vinorelbine-loaded erythrocytes and free vinorelbine. Result The modified hypotonic preswelling technique is an effective method to establish carrier erythro-cytes and vinrelbine-loaded erythrocytes with the drug loading ratio approximating 70.92%, and may be kept for 5 d in vi-tro. During encapsulation, the morphology and characteristics of erythrocytes remained stable, and carrier erythrocytes could release vinorelbine sustainably, and approaching 100%vinorelbine was released from carrier erythrocytes at 48 h. With the dose of vinorelbine at 0.0125 mg/ml and 0.025 mg/ml, vinorelbine-loaded erythrocytes appeared better cell pro-liferation inhibition than free vinorelbine when incubated with A549 for 48 h （P〉0.05）;the dose of vinorelbine in vinore-line-loaded erythrocytes group was lower than free vinorelbine group when the inhibition ratio was same. Conclusion The carrier erythrocytes established in this research is robust and stable, with potentially sustainable release, which im-proves efficacy under specific drug concentrations.