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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
Disulfide-linked liposomes: effective delivery vehicle for Bcl-2 antisense oligodeoxyribonucleotide G3139
Wanlop Weecharangsan1, Bo Yu, Shujun Liu
1College of Pharmacy, The Ohio State University, 542 LM Parks Hall, 500 W. 12th Ave, Columbus, OH 43210, USA.
Background:
Disulfide-linked oligodeoxyribonucleotide (ODN) liposomes were formulated and evaluated for the delivery of antisense ODN G3139 in KB human oral carcinoma cells.
Materials And Methods:
Liposomes composed of 1,2-di-(9Z-octadecenoyl)-3-trimethylammo-nium-propane (DOTAP)/egg phosphatidylcholine/alpha-tocopheryl polyethylene glycol 1000 succinate were incorporated with hydrophobized disulfide-linked ODN. Disulfide-linked ODN liposomes were characterized for their size, ODN intracellular delivery, Bcl-2 mRNA and protein expression, growth inhibition, and chemosensitization.
Results:
Intracellular delivery of ODN with disulfide-linked ODN liposomes was more efficient than that with non-liposomal hydrophobized disulfide-linked ODN. Treatment of the cells with disulfide-linked ODN liposomes resulted in efficient Bcl-2 down-regulation greater than that with hydrophobized disulfide-linked ODN and consistent with that of cellular growth inhibition and the sensitization to daunorubicin in KB cells. Disulfide-linked ODN liposomes exhibited superior colloidal stability during 5-week storage.
Conclusion:
Disulfide-linked liposomes are effective delivery vehicles for antisense ODN.
Insights
Disulfide-linked liposomes efficiently deliver antisense oligodeoxyribonucleotides (ODN) into oral cancer cells, enhancing drug sensitivity and inhibiting tumor growth. These liposomes show improved stability and cellular uptake compared to other methods.
Area of Science:
- Nanomedicine
- Lipid-based drug delivery systems
- Antisense oligonucleotide therapeutics
Background:
- Antisense oligodeoxyribonucleotides (ODN) show promise for cancer therapy but require effective delivery systems.
- KB human oral carcinoma cells were used as a model system.
- Disulfide-linked ODN liposomes were investigated for enhanced therapeutic potential.
Purpose of the Study:
- To formulate and evaluate disulfide-linked oligodeoxyribonucleotide (ODN) liposomes for antisense ODN G3139 delivery.
- To assess the efficiency of ODN intracellular delivery and its impact on cancer cell behavior.
- To determine the stability and efficacy of these novel liposomal formulations.
Main Methods:
- Liposomes were prepared using DOTAP, egg phosphatidylcholine, and alpha-tocopheryl polyethylene glycol 1000 succinate.
- Hydrophobized disulfide-linked ODN was incorporated into the liposomes.
- Characterization included size, intracellular delivery, Bcl-2 expression, growth inhibition, and chemosensitization assays.
Main Results:
- Disulfide-linked ODN liposomes demonstrated more efficient intracellular ODN delivery compared to non-liposomal formulations.
- Significant Bcl-2 down-regulation, cellular growth inhibition, and sensitization to daunorubicin were observed in KB cells.
- The liposomes exhibited excellent colloidal stability over a 5-week storage period.
Conclusions:
- Disulfide-linked liposomes serve as effective delivery vehicles for antisense ODN.
- This formulation enhances the therapeutic efficacy of antisense ODN in oral carcinoma.
- The improved stability and delivery efficiency offer a promising strategy for cancer treatment.
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