A new in vivo anti-viral assay using microencapsulated infected cell cultures.
Microencapsulation technology makes it possible to encapsulate virus infected human or animal cells in microcapsules with semipermeable membranes. These may be implanted intraperitoneally into mice which may then be treated with antiviral drugs. The implanted microcapsules may be recovered at various intervals following in vivo treatment and the effect of the drug is evaluated by assaying the virus titers inside the microcapsules. In this paper, the feasibility of this model was tested using microencapsulated human or non-human cells infected with herpes simplex virus type 1. The microcapsules were implanted in the peritoneal cavity of mice, and the effect of systematically administered acyclovir on HSV-1 replication was ascertained. We found that (a) HSV-1 can replicate in both human (A549 and FEMx) and non-human (Vero) cells after they are infected and encapsulated. (b) HSV-1 replication was inhibited by 0.005 microgram/ml to 0.08 mg/ml of acyclovir in the medium when virus producing A549 cells were encapsulated or when they were in monolayers. (c) Acyclovir (20-80 mg/kg), injected twice daily by intraperitoneal, subcutaneous or intravenous routes in mice, significantly inhibited HSV-1 production in encapsulated Vero cells implanted in the peritoneal cavity. The major advantage of this in vivo model is that it can be used to study antivirals in experimental animals in which viruses do not replicate in non-permissive animals. Toxicity, pharmacokinetic and efficacy data may be obtained. It can also be used to test drugs which require activation in vivo to be effective.
Li
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XQ
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, PA 15261.
Gorelik
E
E
Atchison
R W
RW
Ovejera
A
A
Ho
M
M
D000212:Acyclovir / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002214:Capsules; D002455:Cell Division; D002470:Cell Survival; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008545:Melanoma; D051379:Mice; D010539:Permeability; D018139:Simplexvirus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
D002214:Capsules; D000212:Acyclovir