title: Sustained-release nanoART formulation for the treatment of neuroAIDS.
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.
authors.affiliation: Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
authors.forename: Rahul Dev
authors.initials: RD
authors.lastname: Jayant
authors.affiliation: Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
authors.forename: Venkata S R
authors.initials: VS
authors.lastname: Atluri
authors.affiliation: Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
authors.forename: Marisela
authors.initials: M
authors.lastname: Agudelo
authors.affiliation: Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
authors.forename: Vidya
authors.initials: V
authors.lastname: Sagar
authors.affiliation: Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
authors.forename: Ajeet
authors.initials: A
authors.lastname: Kaushik
authors.affiliation: Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
authors.forename: Madhavan
authors.initials: M
authors.lastname: Nair
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy*; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D058185:Magnetite Nanoparticles / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D044966:Anti-Retroviral Agents; D003692:Delayed-Action Preparations; D058185:Magnetite Nanoparticles
keywords: anti-HIV drug; blood–brain barriers; latency; layer-by-layer; magnetic nanocarriers; neuroAIDS; sustained release