Liposome-Mediated Chemotherapeutic Delivery Is Synergistically Enhanced by Ternary Lipid Compositions and Cationic Lipids
| Autor: | Carl C. Hayden, Zachary I. Imam, Jeanne C. Stachowiak, Morgan Mendicino, Andrea N. Trementozzi |
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| Rok vydání: | 2019 |
| Předmět: |
Drug
Surface Properties media_common.quotation_subject Cell 02 engineering and technology 010402 general chemistry 01 natural sciences Article Propane Electrochemistry medicine General Materials Science Doxorubicin Lipid bilayer Spectroscopy media_common Liposome Chemistry Cationic polymerization Surfaces and Interfaces 021001 nanoscience & nanotechnology Condensed Matter Physics Small molecule 0104 chemical sciences medicine.anatomical_structure Membrane Liposomes Biophysics 0210 nano-technology medicine.drug |
| Zdroj: | Langmuir |
| ISSN: | 1520-5827 0743-7463 |
| DOI: | 10.1021/acs.langmuir.9b01965 |
| Popis: | Most small molecule chemotherapeutics must cross one or more cellular membrane barriers to reach their biochemical targets. Owing to the relatively low solubility of chemotherapeutics in the lipid membrane environment, high doses are often required to achieve a therapeutic effect. The resulting systemic toxicity has motivated efforts to improve the efficiency of chemotherapeutic delivery to the cellular interior. Toward this end, liposomes containing lipids with cationic head groups have been shown to permeabilize cellular membranes, resulting in the more efficient release of encapsulated drugs into the cytoplasm. However, the high concentrations of cationic lipids required to achieve efficient delivery remain a key limitation, frequently resulting in toxicity. Toward overcoming this limitation, here, we investigate the ability of ternary lipid mixtures to enhance liposomal delivery. Specifically, we investigate the delivery of the chemotherapeutic, doxorubicin, using ternary liposomes that are homogeneous at physiological temperature but have the potential to undergo membrane phase separation upon contact with the cell surface. This approach, which relies upon the ability of membrane phase boundaries to promote drug release, provides a novel method for reducing the overall concentration of cationic lipids required for efficient delivery. Our results show that this approach improves the performance of doxorubicin by up to 5-fold in comparison to the delivery of the same drug by conventional liposomes. These data demonstrate that ternary lipid compositions and cationic lipids can be combined synergistically to substantially improve the efficiency of chemotherapeutic delivery in vitro. |
| Databáze: | OpenAIRE |
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