Journal
MOLECULAR PHARMACEUTICS
Volume 6, Issue 6, Pages 1848-1855Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp900150g
Keywords
Liposomes; antisense oligonucleotide; G3139; Bcl-2; lipoplex; human serum albumin; drug delivery; cancer
Funding
- NIH [CA-135243]
- NSF [EEC-0425626]
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Human serum albumin (HSA)-coated liposomal formulations were synthesized and evaluated for the delivery of antisense oligodeoxyribonucleotide (ODN) 63139 in KB human oral carcinoma cells. Liposomes composed of dimethyldioctadecylammonium bromide/egg phosphatidylcholine/alpha-tocopheryl polyethylene glycol 1000 succinate (58:40:2 molar ratio) complexed with G3139 and coated with HSA were investigated for Bcl-2 downregulating activity. Cellular uptake of HSA-coated liposome-ODN complexes was more efficient than the uncoated liposome-ODN complexes. Treatment of the cells with HSA-coated liposome-ODN complexes resulted in efficient Bcl-2 mRNA downregulation that was approximately 3-fold greater than with uncoated liposomes (p < 0.05) and 6-fold greater than with free ODN. The transfection efficiency of liposome-ODN complexes coated with HSA was dependent on the concentration of HSA used and on the contents of alpha-helix and beta-strand in HSA. HSA-coated liposomes are effective delivery vehicles for antisense ODN.
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