Studies on the effects of borneol on the distribution of azidothymidine palmitate liposomes in mice

摘要

In order to evaluate whether borneol can promote azidothymidine palmitate (AZTP) through blood-brain barrier in mice, in present study, soybean phosphatidylcholine (SPC)/cholesterol(CH)/borneol(B) (80:10:10, mol/mol/mol) (10%B-AZTPL) and SPC/CH/B(80:20:0) (AZTP-CL) incorporated AZTP were prepared by ethanol injection method followed by ultrasonic-dispersion and characterized by entrapped efficiencies more than 96% and mean diameter less than 120nm, respectively; Zeta potential about-27.5mv in both. Then, as a dose of 15.85 mg·kg-1 AZT solution and 30.0mg·kg-1 (at equimolar doses) AZTP in two liposomes were injected intravenously via tail vein in KM mice, respectively. The distributions of AZT in plasma and various organs were determinated by reversed phase HPLC after i. v. administration and evaluated by AZT uptake volume calculated in different tissues. Compared to 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 drug 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 1.69 and decreased 0.7 times (p<0.05) as that of AZT solution, respectively. In conclusion, borneol as an infiltration agent to promote the transient opening of blood-brain barrier and conduct other substances into brain, the modification of the 10% (mol/mol) borneol addition upon AZTP liposomes indeed achieved its "resuscitation-inducing" and "primer medicine", significantly increased AZTP permeability of blood-brain barrier into brain tissues. These results indicate that 10% borneol modified AZTP liposomes is expected to become a convenient and easy method for HIV encephalopathy therapy.