AEGiS-11IAC: Targeting lymphoid organs in HIV disease.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Targeting lymphoid organs in HIV disease.

Int Conf AIDS 1996 Jul 7-12; 11:213 (abstract no. Th.A.155)
Harvie P, Dusserre N, Desormeaux A, Tremblay M, Beauchamp D, Bergeron MG; Centre de Recherche en Infectiologie, Centre Hospitalier de I'Universite Laval, Ste-Foy, Quebec, Canada. Fax: (418) 654-2715.

OBJECTIVE: To improve the targeting of antiviral agents to lymphoid tissues with the use of liposomes as a drug delivery system.

METHODS: The pharmacokinetic properties and tissue distribution of free and liposome-encapsulated antiviral agents (ddC, ddI, foscarnet) have been evaluated in rodents following the administration of a single bolus dose. Drug and lipid levels were monitored in plasma and lymphoid tissues with radioactive tracers.

RESULTS: Results clearly demonstrated that the incorporation of antiviral agents into liposomes improves the drug accumulation in organs of the reticuloendothelial system following intravenous administration in rodents. Of particular interest, we showed that the AUC of liposomal foscarnet in the lymph nodes was 8 times greater than that of the free agent. Moreover, the tissue distribution profile of labeled lipids showed that the use of conventional liposomes allowed efficient targeting of lymph nodes and macrophage-rich tissues for up to at least 24 h post-injection. An extended plasma half-life and a progressive uptake by the spleen was observed upon encapsulation of ddI in liposomes sterically stabilized with polyethylene glycol. On the other hand, the entrapment of antiviral agents into liposomes resulted in a significant improvement of the pharmacokinetic properties of drugs. A large reduction of the systemic clearance of the antiviral agents was observed upon incorporation into liposomes.

CONCLUSION: The use of liposomes represents a convenient strategy to increase the amount of drugs at specific sites of infection, more particularly in lymphoid organs. Such targeted delivery system should hopefully reduce the dissemination of HIV from the lymphoid tissues and preserve the follicular dendritic cells microenvironment that will likely protect the infected host from developing the characteristic immunodeficient state. The improved pharmacology of liposomal drugs could reduce the dose and the frequency of administration of antiviral agents used in conventional therapy.

Keywords: AEGIS, Didanosine, HIV, Antiviral Agents, Liposomes, Foscarnet, Lymphoid Tissue, HIV Protease Inhibitors, Tissue Distribution, Drug Delivery Systems, Biological Transport, HIV Core Protein p24, Zalcitabine, Lymph Nodes, Macrophages, Polyethylene Glycols, Injections, Spleen, pharmacokinetics, ICA11

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ThA155