Encapsulation of therapeutic nucleoside hydrolase in functionalised nanocapsules.

TitleEncapsulation of therapeutic nucleoside hydrolase in functionalised nanocapsules.
Publication TypeJournal Article
Year of Publication2005
AuthorsHuysmans, G., A. Ranquin, L. Wyns, J. Steyaert, and P. Van Gelder
JournalJ Control Release
Volume102
Issue1
Pagination171-9
Date Published2005 Jan 20
ISSN0168-3659
KeywordsDrug Compounding, Liposomes, N-Glycosyl Hydrolases, Nanostructures, Prodrugs, Substrate Specificity
Abstract

Liposomes are introduced as encapsulating carrier for prodrug activating enzymes. Inosine√£-adenosine√£-guanosine preferring nucleoside hydrolase of Trypanosoma vivax, a potential prodrug activating enzyme, was encapsulated in porin functionalized dioleyl-phosphatidylglycerol/egg-phosphatidylglycerol (DOPC/EPG) liposomes. Reactors had radiuses in the nanometer scale. First, transport of nucleosides through general diffusion porins OmpF and PhoE was measured in swelling assays, after which fully functional nanoreactors were developed. Enzyme catalysis of p-nitrophenylriboside, a substrate analogue for nucleoside hydrolases, was significantly higher in permeabilized vesicles than in control vesicles without porins. Residual activity of control vesicles possibly resides in an interaction between the enzyme and the liposomes. This interaction was not of electrostatic nature, since it remained unaffected after the addition of high salt or after perturbation of liposome surface charge and charge density. With these vesicles, we have introduced a new strategy for prodrug therapy, combining the benefits of ADEPT and liposome targeting strategies.

DOI10.1016/j.jconrel.2004.10.002
Alternate JournalJ Control Release
PubMed ID15653143