Sustained-release nanoART formulation for the treatment of neuroAIDS

Int J Nanomedicine. 2015 Feb 4;10:1077-93. doi: 10.2147/IJN.S76517. eCollection 2015.


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.

Keywords: anti-HIV drug; blood–brain barriers; latency; layer-by-layer; magnetic nanocarriers; neuroAIDS; sustained release.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Dementia Complex / drug therapy*
  • Anti-Retroviral Agents* / pharmacokinetics
  • Anti-Retroviral Agents* / pharmacology
  • Anti-Retroviral Agents* / therapeutic use
  • Anti-Retroviral Agents* / toxicity
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Delayed-Action Preparations / therapeutic use
  • Delayed-Action Preparations / toxicity
  • Humans
  • Magnetite Nanoparticles* / therapeutic use
  • Magnetite Nanoparticles* / toxicity


  • Anti-Retroviral Agents
  • Delayed-Action Preparations
  • Magnetite Nanoparticles