摘要
目的:研究N-三甲基壳聚糖(TMC)的季铵化程度(DQ)对TMC包衣脂质体安全性的影响规律,为其作为药物载体的安全应用提供实验依据。方法:分别制备未包衣的脂质体及用不同DQ的TMC(TMC20,TMC40及TMC60)包衣的脂质体;采用静脉注射及腹腔注射,对其小鼠急性毒性进行考察,分别得到静脉注射及腹腔注射的LD_(50);对其注射刺激性、过敏性及溶血性进行考察。结果:未包衣脂质体及TMC20,TMC40、TMC60包衣脂质体静脉注射的LD_(50)及95%置信限分别为808.1(676.4~1 009.5)、721.9(584.0~971.9)、319.1(261.9~399.0)、224.1(178.8~302.6)mg·kg^(-1);未包衣脂质体及各种包衣脂质体腹腔注射的LD_(50)及95%置信限分别为1 158.3(958.4~1 443.0)、1 109.5(899.9~1 415.4)、573.7(480.2~716.6)、342.3(269.7~534.2)mg·kg^(-1)。与未包衣的脂质体相比,TMC20包衣后小鼠静脉注射及腹腔注射的LD_(50)无明显变化(P>0.05),而TMC40及TMC60包衣脂质体的相应LD_(50)有较明显的降低(P<0.05);包衣脂质体间相比较,相应LD_(50)随着DQ的增加而逐渐下降(P<0.05);在实验剂量时,各组脂质体均无注射刺激性、过敏性及溶血性。结论:TMC的DQ对其包衣的脂质体生物安全性有较明显的影响,DQ越大,LD_(50)越低。
Objective： To evaluate the effect of quaternization degree （DQ） of N-trimethyl chitosan （TMC） on the bio-safety of TMC-coating liposomes to lay the foundation for tile TMC application in the drug vehicles. Method： Un-coated liposomes and TMC- coated liposomes with various DQ were prepared. The acute toxicity in mice of the liposomes by iv and ip was studied and LDs0 was ob-tained. The intravenous stimulation, injection anaphylaxis and hemolysis were investigated as well. Result： LDso with 95% confidence limits （iv） of un-coated liposomes and TMC20, TMCA0 and TMC60-coated liposomes was 808.1（676.4-1 009.5 ）, 721.9 （584.0- 971.9）, 319, 1 （261.9-399.0） and 224.1 （178.8-302.6） mg· kg-1, respectively. LDs0 with 95% confidence limits （ip） of the above liposomes was 1 158.3 （958.4-1 443.0） , 1 109.5 （ 899.9-1 415.4）, 573.7 （480.2-716.6） and 342.3 （ 269.7-534.2 ） nag · kg - 1 , respectively. Compared with that of un-coated liposomes, LDs0 of TMC20-coated liposomes was without significant difference （ P 〉 0.05） , while that of TMC40-coated and TMC60-coated liposomes showed significant decrease （ P 〈 0.05 ）. Among the TMC-coated liposomes, LDs0 was decreased with the increase of DQ of TMC （ P 〈 0.05 ）. Meanwhile, all liposomes showed no intravenous stimula- tion, injection anaphylaxis and hemolysis at the testing concentration. Conclusion： DQ of TMC has significant effect on the bio-safety of TMC-coated liposomes.
出处
《中国药师》
CAS
2013年第9期1282-1284,共3页
China Pharmacist
