| Effect of nucleoside analogues and oligonucleotides on hydrolysis of liposomal phospholipids. | |
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MedLine Citation:
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PMID: 11058809 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The hydrolysis of the bilayer forming phospholipids resulting first of all in lysophospholipids and fatty acids is one limiting factor determining the shelf-life of liposomes. In several studies the influence of pH, buffer, lipid composition and other parameters on the hydrolysis of phospholipids have been demonstrated, but the influence of drugs has not yet been investigated systematically. In this study the influence of nucleoside analogues, especially 2', 2'-difluoro 2'-deoxycytidine (gemcitabine, dFdC) on the degradation of phospholipids was elucidated in more detail. It could be demonstrated that the interaction of dFdC with phospholipid bilayers promotes the hydrolysis of phospholipids in a concentration-dependent manner. Obviously two parts of the molecule, the amino group bound to the pyrimidine moiety and the 2', 2'-difluoro-2'-deoxyribose, seem to be responsible for the forced phospholipid hydrolysis. The dFdC-induced hydrolysis of phospholipids was influenced by pH, buffer, lipid composition and different anions. Optimization of the above parameters resulted in prolonged shelf-life of dFdC liposome dispersions, which is an important prerequisite for clinical practice. |
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Authors:
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R Moog; M Brandl; R Schubert; C Unger; U Massing |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of pharmaceutics Volume: 206 ISSN: 0378-5173 ISO Abbreviation: Int J Pharm Publication Date: 2000 Sep |
Date Detail:
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Created Date: 2000-11-20 Completed Date: 2000-11-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 43-53 Citation Subset: IM |
Affiliation:
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Tumor Biology Center, Department of Clinical Research, Breisacher Strasse 117, 79106, Freiburg, Germany. reginam@farmasi.uit.no |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anions Antimetabolites, Antineoplastic / administration & dosage Buffers Deoxycytidine / administration & dosage, analogs & derivatives Hydrogen-Ion Concentration Hydrolysis Lipid Bilayers / metabolism* Liposomes Lysophospholipids / administration & dosage*, chemistry Nucleosides / administration & dosage*, chemistry Oligonucleotides / administration & dosage*, chemistry |
| Chemical | |
Reg. No./Substance:
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0/Anions; 0/Antimetabolites, Antineoplastic; 0/Buffers; 0/Lipid Bilayers; 0/Liposomes; 0/Lysophospholipids; 0/Nucleosides; 0/Oligonucleotides; 103882-84-4/gemcitabine; 951-77-9/Deoxycytidine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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