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

• 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
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2004.01.001

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.