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A novel pH-sensitive liposome formulation containing oleyl alcohol.
Jennifer J Sudimack1, Wenjin Guo, Werner Tjarks
1Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Biochimica Et Biophysica Acta
|July 9, 2002
Summary
New pH-sensitive liposomes overcome serum instability and enhance cancer drug delivery. These novel formulations show improved stability and targeted delivery of therapeutic agents, demonstrating promise for cancer treatment.
Area of Science:
- Nanotechnology
- Materials Science
- Biomedical Engineering
Background:
- First-generation pH-sensitive liposomes based on dioleoylphosphatidylethanolamine (DOPE) exhibit reduced fusogenicity in serum.
- There is a need for serum-resistant pH-sensitive liposomes for effective drug delivery.
Purpose of the Study:
- To design and evaluate novel serum-resistant pH-sensitive liposome formulations.
- To assess the stability, pH-triggered destabilization, and drug delivery capabilities of these liposomes.
Main Methods:
- Formulation of pH-sensitive liposomes using egg phosphatidylcholine (PC), cholesteryl hemisuccinate (CHEMS), oleyl alcohol (OAlc), and Tween-80 (T-80).
- Evaluation of liposome stability at pH 7.4 and destabilization at acidic pH using calcein dequenching and particle size analysis.
- Assessment of serum resistance in the presence of 10% serum and membrane fusion using an octadecylrhodamine B chloride (R(18)) lipid-mixing assay.
- In vitro evaluation of intracellular delivery and cytotoxicity of entrapped cytosine-beta-D-arabinofuranoside (araC) in KB oral cancer cells using folate receptor (FR)-targeted liposomes.
Main Results:
- The novel liposome formulations demonstrated excellent stability at pH 7.4 and rapid destabilization upon acidification.
- Adjusting the ratios of T-80 and OAlc allowed for regulation of liposome stability and pH-sensitivity.
- Formulations exhibited significantly improved pH-sensitive properties in the presence of serum compared to DOPE-based liposomes.
- FR-targeted OAlc-based pH-sensitive liposomes achieved a 17-fold greater FR-dependent cytotoxicity in KB cells compared to non-pH-sensitive liposomes.
Conclusions:
- Novel pH-sensitive liposomes based on PC, CHEMS, OAlc, and T-80 offer enhanced serum resistance and tunable pH-triggered destabilization.
- These liposomes are effective in delivering therapeutic agents intracellularly, particularly when targeted via the folate receptor.
- The developed liposomes represent a promising platform for the delivery of membrane-impermeable therapeutic agents in cancer therapy.