Encapsulation of therapeutic nucleoside hydrolase in functionalised nanocapsules.
Liposomes are introduced as encapsulating carrier for prodrug activating enzymes. Inosineã-adenosineã-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.
Huysmans
Gerard
G
Department of Molecular and Cellular Interactions, Flanders Interuniversity Institute for Biotechnology (VIB) and Free University Brussels, Pleinlaan 2, 1050 Brussels, Belgium.
Ranquin
An
A
Wyns
Lode
L
Steyaert
Jan
J
Van Gelder
Patrick
P
D004339:Drug Compounding / Q000379:methods; D008081:Liposomes; D009699:N-Glycosyl Hydrolases / Q000138:chemical synthesis* / Q000627:therapeutic use*; D049329:Nanostructures / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis / Q000627:therapeutic use; D013379:Substrate Specificity
D008081:Liposomes; D011355:Prodrugs; D009699:N-Glycosyl Hydrolases