摘要
用乳化—热固化法制备了米托蒽醌白蛋白微球，并对其形态、大小及其分布、微粉学性质、载药性能、体外释药、稳定性和体内分布进行了研究。结果表明，该载药微球的平均算术径为０９９μｍ，平均表面径为１２４μｍ，平均容积径为１４４μｍ；表观载药量为２５５８％±０１０１％；有效载药量为１５０３％±０１２７％；包封率为９２８２％±４６０％；体外释药符合双相动力学规律，释药方程为１－Ｑ＝０６４２８ｅ－０２１３２ｔ＋０３９８８ｅ－０００１５０ｔ（γ１＝－０９９５１，γ２＝－０９９８２）；Ｔ１／２α＝３２５０ｈ，Ｔ１／２β＝４６１７ｈ；室温放置３个月，微球形态、药物含量等均无明显变化。ＨＰＬＣ测定表明，小鼠尾ｉｖ该微球２０ｍｉｎ内即有７７６％±１３８％的药物浓集于肝脏，具有明显的肝靶向性。提示米托蒽醌白蛋白微球有可能提高米托蒽醌的抗肝癌效果和降低其全身毒副作用。
An optimum procedure was established for preparing mitoxantrone albumin microspheres (DHAQ BSA MS) with emulsion heating solidification. The morphology, diameters, drug loading, release characteristics, stability and its distribution in vivo of the drug loaded albumin microspheres were studied. The results showed that the surface was regular, the average diameter was 0 99 μm, mean surface diameter was 1 24 μm and mean volume diameter was 1 44 μm, apprarent drug loading was 2 558±0 101 μg·mg -1 ( n =5), effective drug loading was 1 503%±0 127% ( n =5), embeding ratio was 92 82%±6 48% ( n =5), and the release characteristics were in accord with “biphase kinetics equation”: 1-Q=0 6428e -0 2132t +0 3988e -0 00150t (γ 1=-0 9951, γ 2=-0 9982); T 1/2 α=3 250 h, T 1/2 β=461 7 h. The stability of the drug loadeled albumin microspheres was good after three months storage at room temprebure. The results determined by HPLC showed that the drug accumulated about 77 6%±1 38% of the dose in the liver 20 minutes after intravenous injecton to mice. This indicates that DHAQ BSA MS showed remakable targeting for liver, and it seems to have important value for increasing the antihepatoma effect and decreasing the toxicity of mitoxantrone.
出处
《药学学报》
CAS
CSCD
北大核心
1997年第1期72-78,共7页
Acta Pharmaceutica Sinica
