Abstract
A novel approach was developed for the coencapsulation of an anti-HIV drug (tenofovir) and a latency-breaking agent (vorinostat), using magnetically guided layer-by-layer (LbL) assembled nanocarriers for the treatment of neuroAIDS. Ultrasmall iron oxide (Fe3O4) nanoparticles (10±3 nm) were synthesized and characterized. The LbL technique was used to achieve a sustained release profile, and application of 2 bilayers ([tenofovir+dextran sulphate]2+vorinostat) to magnetic nanoparticles resulted in a 2.8 times increase in drug (tenofovir) loading and also resulted in an increase in the drug release period by 30-fold, with 100% drug release in sustained manner over a period of 5 days with the simultaneous stimulation of latent HIV expression. Nanoformulation showed a good blood-brain barrier transmigration ability (37.95%±1.5%) with good in vitro antiviral efficacy (~33% reduction of p24 level) over a period of 5 days after HIV infection in primary human astrocytes, with good cell viability (>90%). Hence, LbL arrangements of drugs on magnetic nanoparticles provides sustained release and, therefore, may improve the patient's adherence to therapy and lead to better compliance.