Liposomes for targeted delivery of radioiodinated IVdU and 3-CH3-IVdU for non-invasive detection of herpes simplex virus encephalitis in mice.
Liposomal encapsulation of radioiodinated anti-herpes nucleosides was undertaken to reduce metabolic inactivation and increase blood-brain barrier penetration of the nucleosides, and so provide formulations suitable for use in the non-invasive scintigraphic diagnosis of herpes simplex encephalitis (HSE). The nucleosides investigated were [125I]-IVdU and its more lipophilic 3-methyl derivative, and they were encapsulated in phosphatidylcholine:cholesterol:sulfatide liposomes with an efficiency of 4.4% and 1.7% respectively. The encapsulation of IVdU reduced in vitro phosphorolysis (by 31% in serum at 25 degrees C over 3 hr as compared with non-encapsulated IVdU), and markedly increased in vivo stability (fifty-fold greater than that of free drug). In normal mice, higher radioactivity levels were observed in most tissues and there was prolonged, constant blood and brain uptake. Biodistribution of liposomal IVdU in herpes simplex virus (HSV) infected animals was similar, but somewhat lower concentrations were attained. Liposomal encapsulation of [125I]-3-CH3-IVdU produced less dramatic changes in tissue distribution in either healthy or HSV infected mice, as compared with the non-encapsulated drug. Whilst, in HSV infected mice, liposomal encapsulation of both drugs caused increased uptake by spleen, liver and lung, the uptake by brain was still too low for detection by whole-body scintigraphy.
Stathaki
S
S
Division of Bionucleonics and Radiopharmacy, Faculty of Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Wiebe
L I
LI
Knaus
E E
EE
Rogers
J A
JA
Tovell
D
D
Tyrrell
D L
DL
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002784:Cholesterol; D004355:Drug Stability; D004660:Encephalitis / Q000175:diagnosis*; D006561:Herpes Simplex / Q000175:diagnosis*; D007065:Idoxuridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008081:Liposomes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010713:Phosphatidylcholines; D018139:Simplexvirus; D013433:Sulfoglycosphingolipids; D013696:Temperature
D007457:Iodine Radioisotopes; D008081:Liposomes; D010713:Phosphatidylcholines; D013433:Sulfoglycosphingolipids; C060866:3-methyl-5-(2-iodovinyl)-2'-deoxyuridine; C030360:5-(2-iodovinyl)-2'-deoxyuridine; D002784:Cholesterol; D007065:Idoxuridine