The potential use of liposome-mediated antiviral therapy

Koff, Wayne C.; Fidler, Isaiah J.

doi:10.1016/0166-3542(85)90050-6

Cited by 44 publications

(14 citation statements)

References 61 publications

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“…This can be done either by an active scheme in which a targeting ligand is employed or by exploiting the known capacity of macrophages to take up liposomes. If the latter approach is taken, viral diseases that infect the macrophage would be ideal targets for such therapy (16). Clearly, PF and PA appear to be good candidates for liposome encapsulation for therapy of virally infected macrophages.…”

Section: Discussionmentioning

confidence: 99%

Increased efficacy of phosphonoformate and phosphonoacetate inhibition of herpes simplex virus type 2 replication by encapsulation in liposomes

Szoka

Chu

1988

Antimicrob Agents Chemother

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Phosphonoformate and phosphonoacetate encapsulated in liposomes have substantially greater activity against herpes simplex virus type 2 in Vero cell tissue culture than the nonencapsulated compounds at the same dose. Encapsulation of phosphonoformate in liposomes resulted in a 30-fold increase of the antiviral effect with no increase in cytotoxicity measured by inhibition of thymidine incorporation into normal Vero cells. Thus, the selectivity of the liposomal drug increased 27-fold compared with the nonencapsulated compound. Liposome encapsulation of phosphonoacetate at a ratio of 0.3 mumol/mumol of lipid resulted in a 150-fold increase of antiviral activity with a concomitant 250-fold increase in cytotoxicity. However, the selectivity of phosphonoacetate could be increased by reducing the drug-to-lipid ratio. Liposome uptake by Vero cells, measured by the cell association of a nonexchangeable radiolabeled lipid, plateaued after 24 h of incubation and saturated at 60 nmol of lipid per mg of cellular protein at a lipid concentration of 300 microM. The saturation of liposome uptake on the Vero cells may account for the 27-fold increase in selectivity observed with the liposomal phosphonoformate. The greater activity of the encapsulated phosphono compounds is most likely due to their increased transport into the cytoplasm; this occurs subsequent to the uptake and processing of the liposome in the lysosomes of the cell. Liposome encapsulation of these agents may result in superior efficacy against viral infections residing in endocytotically and phagocytically active cells such as macrophages.

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Section: Discussionmentioning

confidence: 99%

Increased efficacy of phosphonoformate and phosphonoacetate inhibition of herpes simplex virus type 2 replication by encapsulation in liposomes

Szoka

Chu

1988

Antimicrob Agents Chemother

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“…Only by improving our understanding ofthe many factors involved in the disease process and undertaking concomitant studies on pharmacokinetics/pharmacodynamics will it become possible to design effective chemotherapeutic regimens. Technology is advancing regarding the targeting of drugs to the site of infection by using prod rugs (Krenitsky et al, 1984), by using protein carriers (Fiume et al, 1988), by modifying drugs to resist metabolic degradation, by use of liposomes or polymers to encapsulate/allow slow or pulse release (Canonico et al, 1984;Kende et al, 1985;Koff and Fidler, 1985). These advances in drug delivery will be of particular importance in veterinary practice, since repeated dosing is not always practicable or cost effective.…”

Section: Discussionmentioning

confidence: 99%

Prospects for Antiviral Chemotherapy in Veterinary Medicine: 2. Avian, Piscine, Canine, Porcine, Bovine and Equine Virus Diseases

Rollinson¹

1992

Antivir Chem Chemother

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SummaryThis paper, which is published in two parts, reviews the literature pertaining to antiviral chemotherapy of viruses of veterinary importance. While early reports in the 1970s referred to the chemotherapy of a number of different RNA and DNA viruses, there' was considerable focus in the 1980s, initially on herpesviruses and latterly on retroviruses, and particularly in cats. Details are given of the successful treatments of FeLV and FIV, which have been used as animal models for HIV therapy. 'Therapy of equine, canine, bovine, porcine, avian, and fish diseases is also considered. The high costs of developing and registering a new chemical entity, especially for food species in which extensive toxicity/residue data are required, is the main reason why specific antiviral compounds are not currently available for veterinary use, although some non-specific immune modulators are now emerging. Concurrent availability of appropriate diagnostic tools is a prerequisite for successful veterinary antiviral chemotherapy, as is a greater understanding of the pathogenesis of virus infections in animals and the development of more sophisticated means of drug delivery, appropriate to both food animal species and companion animals (dogs, cats, and horses). Additionally, antiviral agents are valuable as research tools per se, as opposed to solely as chemotherapeutic agents. Part 1 covers the feline virus diseases, while part 2 includes the other viruses~f veterinary importance, in dogs, horses, cattle, pigs, birds, and fish.

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“…Only by improving our understanding ofthe many factors involved in the disease process and undertaking concomitant studies on pharmacokinetics/pharmacodynamics will it become possible to design effective chemotherapeutic regimens. Technology is advancing regarding the targeting of drugs to the site of infection by using prodrugs (Krenitksy et al, 1984), by using protein carriers (Fiume et aI., 1988), by modifying drugs to resist metabolic degradation, by use of liposomes or polymers to encapsulate/allow slow or pulse release (Canonico et al, 1984;Kende et al,1985;Koff and Fidler, 1985). These advances in drug delivery will be of particular importance in veterinary practice, since repeated dosing is not always practicable Orcost effective.…”

Section: Discussionmentioning

confidence: 99%

Prospects for Antiviral Chemotherapy in Veterinary Medicine: 1. Feline Virus Diseases

Rollinson¹

1992

Antivir Chem Chemother

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This paper, which is published in two parts, reviews the literature pertaining to antiviral chemotherapy of viruses of veterinary importance. While early reports in the 1970s referred to the chemotherapy of a number of different RNA and DNA viruses, there was considerable focus in the 1980s, initially on herpesviruses and latterly on retroviruses, particularly in cats. Details are given of the successful treatments of FeLV and FIV, which have been used as animal models for HIV therapy. The high costs of developing and registering a new chemical entity, especially for food species, in which extensive toxicity/residue data are required, is the main reason why specific antiviral compounds are not currently available for veterinary use, although some non-specific immune modulators are now emerging. Concurrent availability of appropriate diagnostic tools is a prerequisite for successful veterinary antiviral chemotherapy, as is a greater understanding of the pathogenesis of virus infections in animals and the development of more sophisticated means of drug delivery, appropriate to both food animal species and companion animals. Additionally, antiviral agents are valuable as research tools per se, as opposed to solely as chemotherapeutic agents.

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The potential use of liposome-mediated antiviral therapy

Cited by 44 publications

References 61 publications

Increased efficacy of phosphonoformate and phosphonoacetate inhibition of herpes simplex virus type 2 replication by encapsulation in liposomes

Increased efficacy of phosphonoformate and phosphonoacetate inhibition of herpes simplex virus type 2 replication by encapsulation in liposomes

Prospects for Antiviral Chemotherapy in Veterinary Medicine: 2. Avian, Piscine, Canine, Porcine, Bovine and Equine Virus Diseases

Prospects for Antiviral Chemotherapy in Veterinary Medicine: 1. Feline Virus Diseases

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