Linked Life Data

2160335

Source:http://linkedlifedata.com/resource/pubmed/id/2160335

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1990-6-27
pubmed:abstractText
Liposomes can be used as carriers of drugs in the treatment of viral, bacterial and protozoal infections. The potential for liposome-mediated therapy of Mycobacterium avium-intracellulare complex infections, one of the most common opportunistic infections in AIDS, is currently under study. Here, we have investigated the effect of the lipid-soluble antimycobacterial drugs ansamycin, clofazimine and CGP7040 on the thermotropic behavior of liposomes composed of dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylglycerol (DPPG) using differential scanning calorimetry (DSC). In the presence of ansamycin (rifabutine), the peak gel-liquid crystalline phase transition temperature (Tm) of DPPG was reduced, as was the sub-transition temperature (Ts), whereas the Tm of DPPC was reduced only slightly. The temperature of the pre-transition (Tp) of DPPC was lowered, while the pre-transition of DPPG was abolished. Ansamycin also caused the broadening of the transition endotherm of both lipids. Equilibration of the drug/lipid complex for 1 or 5 days produced different thermotropic behavior. In the presence of clofazimine, the cooperativity of the phase transition of DPPG decreased. Above 10 mol% clofazimine formed two complexes with DPPG, as indicated by two distinguishable peaks in DSC thermograms. The Tm of both peaks were lowered as the mole fraction increased. Clofazimine had minimal interaction with DPPC. In contrast, CGP7040 interacted more effectively with DPPC than with DPPG, causing a reduction of the size of the cooperative unit of DPPC even at 2 mol%. The main transition of DPPC split into 3 peaks at 5 mol% drug. The pre-transition was abolished at all drug concentrations and the sub-transition disappeared at 10 mol% CGP7040. These studies suggest that maximal encapsulation of clofazimine in liposomes would require a highly negatively charged membrane, while that of CGP7040 would necessitate a zwitterionic membrane. We have also investigated the interaction of the water-soluble antibiotic pentamidine, which has been used against Pneumocystis carinii, the most lethal of AIDS-related opportunistic pathogens. Aerosol administration of this drug leads to long-term sequestration of the drug in the lungs. The DPPG/pentamidine complex exhibited a pre-transition at 3.5 degrees C, an endothermic peak at 42 degrees C, and an exothermic peak at 44.5 degrees C, followed by another endothermic peak at 55 degrees C. The exotherm depended on the history of the sample, requiring pre-incubation for several minutes below the 42 degrees C transition. These observations suggest that upon melting of the DPPG chains at 42 degrees C, the DPPG crystallizes as a DPPG/pentamidine complex that melts at 55 degrees C.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1,2-Dipalmitoylphosphatidylcholine, http://linkedlifedata.com/resource/pubmed/chemical/1,2-dipalmitoylphosphatidylglycerol, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antifungal Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antitubercular Agents, http://linkedlifedata.com/resource/pubmed/chemical/CGP 7040, http://linkedlifedata.com/resource/pubmed/chemical/Clofazimine, http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Lipids, http://linkedlifedata.com/resource/pubmed/chemical/Pentamidine, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylglycerols, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids, http://linkedlifedata.com/resource/pubmed/chemical/Rifabutin, http://linkedlifedata.com/resource/pubmed/chemical/Rifamycins
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0009-3084
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
361-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Interaction of antimycobacterial and anti-pneumocystis drugs with phospholipid membranes.
pubmed:affiliation
Cancer Research Institute, University of California, San Francisco 94143-0128.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't