Site-directed decapsulation of bolaamphiphilic vesicles with enzymatic cleavable surface groups
| Autor: | Charles Linder, Sarina Grinberg, Mary Popov, Tal Waner, Bosmat Levi-Hevroni, Richard J. Deckelbaum, Eliahu Heldman |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Light Pyridones Stereochemistry Pharmaceutical Science Mice chemistry.chemical_compound Drug Stability Microscopy Electron Transmission medicine Animals Scattering Radiation Moiety Choline Tissue Distribution Furans Fluorescent Dyes chemistry.chemical_classification Drug Carriers Mice Inbred ICR Molecular Structure Hydrolysis Vesicle Cryoelectron Microscopy Fluoresceins Acetylcholine Enzyme chemistry Biochemistry Covalent bond Injections Intravenous Drug delivery Acetylcholinesterase Methyl group medicine.drug |
| Zdroj: | Journal of Controlled Release. 160:306-314 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2011.12.022 |
| Popis: | Stable nano-sized vesicles with a monolayer encapsulating membrane were prepared from novel bolaamphiphiles with choline ester head groups. The head groups were covalently bound to the alkyl chain of the bolaamphiphiles either via the nitrogen atom of the choline moiety, or via the choline ester's methyl group. Both types of bolaamphiphiles competed with acetylthiocholine for binding to acetylcholine esterase (AChE), yet, only the choline ester head groups bound to the alkyl chain via the nitrogen atom of the choline moiety were hydrolyzed by the enzyme. Likewise, only vesicles composed of bolaamphiphiles with head groups that were hydrolyzed by AChE released their encapsulated material upon exposure to the enzyme. Injection of carboxyfluorescein (CF)-loaded vesicles with cleavable choline ester head groups into mice resulted in the accumulation of CF in tissues that express high AChE activity, including the brain. By comparison, when vesicles with choline ester head groups that are not hydrolyzed by AChE were injected into mice, there was no accumulation of CF in tissues that highly express the enzyme. These results imply that bolaamphiphilic vesicles with surface groups that are substrates to enzymes which are highly expressed in target organs may potentially be used as a drug delivery system with controlled site-directed drug release. |
| Databáze: | OpenAIRE |
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