Journal
International Journal of Nanomedicine
Volume 10, Issue -, Pages 1077-1093Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S76517
Keywords
layer-by-layer; magnetic nanocarriers; blood-brain barriers; neuroAIDS; sustained release; anti-HIV drug; latency
Funding
- National Institutes of Health [1R01MH085259, R01DA034547-01]
- NIH-AIDS Research Program
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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 (similar to 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.
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