Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacytargeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5 0 -triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe 2 O 4 @BaTiO 3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

In spite of significant advances in anti-retroviral (ARV) therapy, the elimination of human immunodeficiency virus (HIV) reservoirs from the periphery and the CNS remains a formidable task. The incapability of ARV to go across the blood-brain-barrier (BBB) after systemic administration makes the brain one of the dominant HIV reservoirs. Thus, screening, monitoring, and elimination of HIV reservoirs from the brain remain a clinically daunting and key task. The practice and investigation of nanomedicine possesses potentials for therapeutics against neuroAIDS. This review highlights the advancements in nanoscience and nanotechnology to design and develop specific sized therapeutic cargo for efficient navigation across BBB so as to recognize and eradicate HIV brain reservoirs. Different navigation and drug release strategies, their biocompatibility and efficacy with related challenges and future prospects are also discussed. This review would be an excellent platform to understand nano-enable multidisciplinary research to formulate efficient nanomedicine for the management of neuroAIDS.

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Blood-brain barrier (BBB) is considered as the primary impediment barrier for most of drugs. Delivering therapeutic agents to brain is still a big challenge by now. In our study, a dual mechanism, receptor mediation combining with external non-invasive magnetic force, was incorporated together into ferrous magnet-based liposome for BBB transmigration enhancement. The homogenous magnetic nanoparticles (MNPs) with size of ~ 10 nm were synthesized and confirmed by TEM and XRD respectively. The classical magnetism assay showed presence of characteristic superparamagnetic property. These MNPs encapsulated in PEGylated fluorescent liposomes as magneto liposomes (ML) showed mono-dispersion ~ 130±10 nm diameter by dynamic laser scattering (DLS) using lipid-extrusion technique. Remarkably, this magnetite encapsulation efficiency of nearly 60% was achieved. And the luminescence and hydrodynamic size of ML was stable for over two months under 4 degree. Additionally, the integrity of ML structure remained unaffected through 120 rounds circulation mimicking human blood fluid. After biocompatibility confirmation by cytotoxicity evaluation, these fluorescent ML was further embedded with Transferrin and applied to in vitro BBB transmigration study in presence or absence of external magnetic force. Comparing with only by magnetic force- or Transferrin receptor-mediated transportation, their synergy resulted in 50–100% increased transmigration without affecting the BBB integrity. Consequently, confocal microscopy and iron concentration in BBB-composed cells further confirmed the higher cellular uptake of ML particles due to synergic effect. Thus, our multi-functional liposomal magnetic nanocarriers possess great potential in particles transmigration across BBB and may have bright future in drug delivery to brain.

The blood-brain barrier (BBB) is a diffusion barrier that has an important role in maintaining a precisely regulated microenvironment protecting the neural tissue from infectious agents and toxins in the circulating system. Compromised BBB integrity plays a major role in the pathogenesis of retroviral associated neurological diseases. Human Immunodeficiency Virus (HIV) infection in the Central Nervous System (CNS) is an early event even before the serodiagnosis for HIV positivity or the initiation of antiretroviral therapy (ART), resulting in neurological complications in many of the infected patients. Macrophages, microglia and astrocytes (in low levels) are the most productively/latently infected cell types within the CNS. In this brief review, we have discussed about the effect of HIV infection and viral proteins on the integrity and function of BBB, which may contribute to the progression of HIV associated neurocognitive disorders.