【摘要】 目的制备冰片修饰齐多夫定棕榈酸酯脂质体,并考察冰片是否能促进齐多夫定棕榈酸酯透过血-脑屏障的作用。方法采用乙醇注入-超声分散法分别制备齐多夫定棕榈酸酯普通脂质体和10%冰片修饰脂质体。小鼠尾静脉注射15.85mg·kg-1齐多夫定溶液剂、30mg·kg-1齐多夫定棕榈酸酯(相当于15.85mg·kg-1齐多夫定)普通脂质体和10%冰片修饰脂质体,并以齐多夫定为指标成分,HPLC测定小鼠血浆和各组织中的药物摄取量。结果齐多夫定棕榈酸酯普通脂质体和冰片修饰脂质体的平均粒径均小于120nm,Zeta电位约为-28.2mV,包封率均在96%以上。与溶液剂比,脑内齐多夫定绝对摄取量由普通脂质体组的1.43倍增加到10%冰片修饰组的1.96倍(P<0.05),冰片修饰组药物的直接入脑量是普通组的3.73倍(P<0.01);肺和肾中药物摄取量分别是溶液剂的1.69和0.7倍,具有显著性变化。结论10%冰片可促进齐多夫定棕榈酸酯脂质体中药物透血-脑屏障转运入脑,显著增加药物脑摄取量,10%冰片修饰齐多夫定棕榈酸酯脂质体可望成为一种简便易行的治疗HIV感染脑部疾病方法。更多还原

【Abstract】 OBJECTIVE To prepare borneol modified azidothymidine palmitate liposomes,and evaluate the effect of borneol on blood-brain barrier penetration of azidothymidine palmitate(AZTP) in mice after i.v.administration.METHODS Soybean phosphatidylcholine(SPC)-cholesterol(CH)-borneol(B)(80:10:10,mol/mol/mol)(10%B-AZTPL) and SPC/CH/B(80:20:0) liposomes(AZTP-CL) containing AZTP were prepared by ethanol injection method followed by ultrasonic-dispersion.Then,15.85 mg·kg-1 AZT solution and 30.0 mg·kg-1 AZTP(at equimolar doses of AZT) in two liposomes were given to KM mice via the tail vein,respectively.The distributions of AZT in plasma and various organs were determined by reversed phase HPLC.AZT guantity contained in different tissues was calculated.RESULTS The mean diameter of two liposomes were both less than 120 nm and encapsulation efficiency more than 96%,Zeta potential about-28.2 mV.Compared with AZT control solution,brain absolute uptake of AZT was increased from 1.43 times of AZTP-CL to 1.96 times(P<0.05) of 10%B-AZTPL.The brain direct transport value of the 10% borneol modified preparation was 3.73 times(P <0.01) as that of common liposomes.The lung and renal uptakes of AZT in 10% borneol modified preparation were also significantly increased by 1.69 times and decreased by 0.7 times(P <0.05) compared with AZT solution,respectively.CONCLUSION 10%(mol/mol) borneol promoted the transient opening of blood-brain barrier and transportation of AZTP into brain,significantly increased AZTP permeability into brain tissues.10% borneol modified AZTP liposomes is expected to become a convenient and easy method for HIV encephalopathy therapy.更多还原