In-vitro evaluation of ion-exchange microspheres for the sustained release of liposomal–adenoviral conjugates

This study looks at the development of a novel combination vector consisting of adenovirus conjugated to liposomes (AL complexes) bound to cation-exchanging microspheres (MAL complexes). With adenovirus having a net negative charge and the liposomes a net positive charge it was possible to modify th...

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Bibliographic Details
Published in:Journal of controlled release 2004-03, Vol.95 (3), p.601-611
Main Authors: Steel, Jason C., Cavanagh, Heather M.A., Burton, Mark A., Dingwall, Daniel, Kalle, Wouter H.J.
Format: Article
Language:English
Subjects:
Adenoviridae - chemistry
Adenoviridae - genetics
Adenoviridae - metabolism
Adenovirus
Administration, Topical
AL and MAL complexes
Animals
beta-Galactosidase - biosynthesis
beta-Galactosidase - genetics
Biological and medical sciences
Delayed-Action Preparations - pharmacokinetics
Drug Evaluation, Preclinical - methods
Gene Expression
General pharmacology
Genetic Therapy - methods
HeLa Cells
Humans
Ion Exchange Resins - chemistry
Ion Exchange Resins - pharmacokinetics
Ion-exchange microspheres
Liposomal–adenoviral conjugates
Liposomes - chemistry
Liposomes - pharmacokinetics
Medical sciences
Microspheres
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Rats
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Summary:This study looks at the development of a novel combination vector consisting of adenovirus conjugated to liposomes (AL complexes) bound to cation-exchanging microspheres (MAL complexes). With adenovirus having a net negative charge and the liposomes a net positive charge it was possible to modify the net charge of the AL complexes by varying the concentrations of adenovirus to liposomes. The modification of the net charge resulted in altered binding and release characteristics. Of the complexes tested, the 5:1 and 2:1 ratio AL complexes were able to be efficiently bound by the microspheres and exhibited sustained release over 24 h. The 1:1 and 1:2 AL complexes, however, bound poorly to the microspheres and were rapidly released. In addition the MAL complexes also were able to reduce the toxicity of the AL complexes, which was seen with the 10:1 ratio. The AL complexes showed considerably more toxicity alone than in combination with microspheres, highlighting a potential benefit of this vector.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2004.01.001