[Study on the characteristics of antisense oligodeoxy-neucleotides-liposomes complex and cellular uptake].
OBJECTIVE
To investigate factors affecting the properties of antisense oligodeoxy nucleotides (ASON)-liposomes complex and their cellular uptake.


METHODS
Three types of blank liposomes were prepared by reverse-phase evaporation vesicles, and the complex were obtained through physical absorption. The light microscope was used to observe morphology characteristics of the complex. Drug loading capacity was analyzed by agarose gel electrophoresis. The transfected cell percentage and means fluorescence intensity were determined by flow cytometric analysis using M3 myeloma cell as a model.


RESULTS
The neutral liposome showed no aggregation while the cationic liposomes appeared some different extent aggregation in different medium when associated antisense oligodeoxynucleotides. The drug loading capacity depended on the ratio of +/- and the cationic charge density on the lipid membrane. The two kinds of cationic liposomes appeared different principles of loading ASON. As far as cellular uptake, The neutral liposomes showed no improvement of cellular uptake of ASON. However, the cationic liposomes were shown to enhance the cellular uptake of ASON if the appropriate +/- charge ratio was used. The optimal cellular uptake was achieved when +/- charge ratio was at 0.5:1 and 1:1 for SA-I liposome and SA-II liposomes, respectively.


CONCLUSIONS
The cationic liposomes improved the loading capacity and cell uptake of antisense oligodeoxynucleotides, which was determined by +/- charge ratio and charge density.
Chen
Hai-liang
HL
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, China.
Chen
Zhi
Z
Liang
Wen-quan
WQ
D000588:Amines / Q000378:metabolism; D001692:Biological Transport; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes / Q000493:pharmacokinetics*; D009101:Multiple Myeloma; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011897:Random Allocation; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000588:Amines; D004337:Drug Carriers; D008081:Liposomes; D020319:Oligodeoxyribonucleotides, Antisense; C009317:stearylamine