Targeting antiviral nucleotide analogues to macrophages

Area of Science:

• Virology
• Immunology
• Drug Delivery Systems

Background:

• Macrophages are key targets for human immunodeficiency virus type 1 (HIV-1) infection.
• Developing targeted antiviral strategies is crucial for effective treatment.
• Nucleoside analogues show promise but require efficient delivery mechanisms.

Purpose of the Study:

• To create a drug targeting system for selective delivery of phosphorylated nucleoside analogues to macrophages.
• To enhance the antiviral activity of nucleoside analogues against immunodeficiency viruses.
• To evaluate the efficacy of erythrocyte-encapsulated antivirals in vitro and in vivo.

Main Methods:

• Encapsulating phosphorylated nucleoside analogues into autologous erythrocytes.
• Modifying erythrocyte membranes to promote macrophage recognition and phagocytosis.
• Testing the efficacy of targeted delivery against HIV-1, feline immunodeficiency virus, and LP-BM5 viruses in vitro and in vivo.

Main Results:

• Targeted delivery of nucleoside analogues to macrophages showed greater inhibition of viral infectivity compared to free administration.
• In vivo administration of 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) encapsulated in erythrocytes reduced LP-BM5 virus infectivity and disease progression in mice.
• A novel drug, AZTp2AZT, encapsulated in erythrocytes, demonstrated significantly enhanced antiviral activity against multiple immunodeficiency viruses.

Conclusions:

• Red blood cells serve as an effective drug targeting system for delivering antivirals to macrophages.
• This strategy enhances the efficiency of antiviral nucleoside analogues.
• The development of targeted drug delivery systems offers new possibilities for antiviral drug design and combination therapies.