基于近红外光响应性的盐酸阿霉素纳米脂质体的制备工艺优化

目的:建立盐酸阿霉素纳米脂质体药物含量的测定方法,并优化其制备工艺。方法:采用紫外-可见分光光度法测定盐酸阿霉素纳米脂质体的药物含量;采用薄膜分散法制备盐酸阿霉素纳米脂质体。以粒径、包封率、载药量为指标,以磷脂与药物质量比(mg/mg)、磷脂与胆固醇质量比(mg/mg)、超声时间(min)为因素,采用星点设计-响应面法优化制备工艺;采用近红外光照射考察盐酸阿霉素纳米脂质体的光热转换效应。结果:盐酸阿霉素检测质量浓度的线性范围为1.01～16.16μg/mL(r=0.999 7),精密度、稳定性、重复性均符合《中国药典》相关要求。最优制备工艺为磷脂与药物质量比13.30∶1(mg/mg)、磷脂与胆固醇质量比4.09∶1(mg/mg)、超声时间10 min。在此工艺条件下,所得的盐酸阿霉素纳米脂质体的粒径、载药量分别为(200.5±25.1)nm、(11.02±0.20)%,与预测值(196.3 nm、10.68%)的相对误差分别为1.82%、1.63%,实测值与预测值一致性良好。于808 nm近红外光照射下,盐酸阿霉素纳米脂质体具有浓度和时间依赖性的光热转换效应。结论:所建含量测定方法简便、准确度较好,优化所得工艺简单、可行。

Optimization of Preparation Technology of Near-infrared Light Response-based Doxorubicin Hydrochloride Nano-liposomes

OBJECTIVE:To establish a methaod for content determination of doxorubicin hydrochloride nano-liposomes,and to optimize its preparation technology.METHODS:The contents of doxorubicin hydrochloride nano-liposomes was determined by UV spectrophotometry.The membrane dispersion method was used to prepare doxorubicin hydrochloride nano-liposomes.Using particle size,encapsulation efficiency and drug-loading amount as indexes,the weight ratio of phospholipid to drug(mg/mg),the weight ratio of phospholipid to cholesterol(mg/mg)and ultrasonic time(min)as factors,central composite design-response surface methodology was used to optimize the preparation technology.The photothermal conversion effect of doxorubicin hydrochloride nano-liposomes was investigated by near infrared irradiation.RESULTS:The linear range of doxorubicin hydrochloride were 1.01-16.16μg/mL(r=0.999 7);precision,stability and reproducibility tests were all in line with the requirments of Chinese Pharmacopoeia.The optimal preparation technology included that the weight ratio of phospholipid to drug was 13.30∶1(mg/mg);the weight ratio of phospholipid to cholesterol was 4.09∶1(mg/mg);the ultrasonic time was 10 min.Under this technology,the particle size and drug-loading amount of doxorubicin hydrochloride nano-liposomes were(200.5±25.1)nm and(11.02±0.20)% ,relative errors of which to predicted value(196.3 nm,10.68% )were 1.82% and 1.63% .The consistency between measured value and predicted value was good.Doxorubicin hydrochloride nano-liposomes exhibited concentrationdependent and time-dependent photothermal conversion characteristics under near infrared irradiation at 808 nm.CONCLUSIONS:Established method is simple and good accuracy.The optimized preparation technology is simple and feasible.