Linked Life Data

16318894

Source:http://linkedlifedata.com/resource/pubmed/id/16318894

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-12-26
pubmed:abstractText
The development of procedures to enhance drug retention in liposomes is important in order to achieve therapeutically optimized rates of drug release from liposomal carriers. In this study, the ability of lipophilic weak base drugs to complex with arylsulfonates resulting in formation of intravesicular precipitates is investigated as a means to enhance drug retention. It is shown that the arylsulfonates benzenesulfonate and hydroxybenzenesulfonate (HBS) induce precipitation of ciprofloxacin and vinorelbine, two representative weak base drugs that are difficult to retain in liposomal systems. The most complete precipitation was observed at pH values corresponding to charge neutralization of the drug-arylsulfonate complex. HBS is shown to be a much more effective precipitating agent than benzenesulfonate. It is also shown that vinorelbine and ciprofloxacin can be loaded into large unilamellar vesicles (LUV) containing the calcium salt of HBS using an ionophore-based loading method. Following drug loading, the formation of intravesicular drug-arylsulfonate precipitates of vinorelbine and ciprofloxacin was observed by cryo-electron microscopy. In vitro release experiments showed substantial improvements in drug retention for both vinorelbine and ciprofloxacin when HBS was present as compared to standard loading procedures employing MgSO4 as the entrapped solute. In vivo release experiments for vinorelbine in NuNu mice indicated a half-time for release for HBS-containing LUV of approximately 30 h, compared to 6.4 h for LUV loaded employing MgSO4. It is suggested that encapsulation procedures employing HBS in the internal medium can improve the retention of drugs that are difficult to retain in liposomes, possibly leading to enhanced therapeutic properties.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0168-3659
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
378-86
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Formation of drug-arylsulfonate complexes inside liposomes: a novel approach to improve drug retention.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, 2146 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3. ig0rz@yahoo.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't