Atazanavir Sulfate

Atazanavir sulfate is a potent and selective azapeptide inhibitor of HIV-1 protease. The drug inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thereby preventing the formation of mature virions. By blocking the protease enzyme, atazanavir prevents the cleavage of viral polyprotein precursors into functional proteins required for viral maturation, resulting in the production of immature, non-infectious viral particles. Atazanavir binds to the active site of HIV-1 protease with high affinity and selectivity, acting as a competitive inhibitor to block the catalytic activity of the enzyme. The drug has an in vitro 50% inhibitory concentration ranging from 2 to 5 nM and is active against both wild-type and some protease inhibitor-resistant HIV-1 strains.
Atazanavir demonstrates a distinct resistance profile compared to other protease inhibitors, and resistance to other protease inhibitors often confers clinically relevant resistance to atazanavir. However, atazanavir does not confer resistance to other protease inhibitors, making it a valuable component of highly active antiretroviral therapy regimens.

Solid lipid nanoparticles were developed for the intranasal delivery of atazanavir and elvitegravir combination antiretroviral therapy to treat NeuroAIDS. PEGylation reduced SLN size by approximately up to 12 percent while maintaining monodispersity and high encapsulation efficiency of over 99 percent for both drugs in their amorphous forms. Increased PEGylation significantly enhanced drug permeability across the nasal mucus barrier by up to 10-fold. Cellular uptake studies using RPMI 2650 nasal epithelial cells indicated that PEGylation did not reduce nanoparticle uptake rates. This study provided proof-of-concept that PEGylated SLNs can enhance nasal mucus permeability of cART without hindering cellular uptake, representing the first formulation study for intranasal delivery of this drug combination to treat NeuroAIDS.

Fig. 2 Nanoparticle size distribution determination and nanoparticle size and morphology examination. (Bazargani A.; et al. 2025)