Targeted Delivery and On-demand Release of HIV Drugs

Highly Active Antiretroviral Therapy (HAART) has resulted in remarkable decline in the morbidity and mortality in AIDS Patients. Nevertheless, inadequate or zero reachability of anti-retro viral (ARV) drugs across the blood brain barrier (BBB) results in viral reservoir in the brain hideout. In recent years, use of nanotechnology in medicine has shown exciting prospect for development of novel drug delivery systems.  However, the existing technologies suffer from the lack of adequate transendothelial penetration before the drugs are engulfed by the reticuloendothelial system (RES) cells as well as the uncertainty of drug release from the carrier if and when the nanocarrier reaches the brain.  So from a drug delivery point of view, a fast and effective way of delivering and releasing the drugs on demand from the carrier in the brain is very much needed to eradicate HIV reservoir. Magnetic or electric fields have been shown separately to exert beneficial effects on the biological systems including brain diseases. Hence we hypothesize that coupling of these two properties using magneto-electric nanoparticles (MENPs) will serve as an effective carrier to deliver and, most importantly, to release the drugs on demand in the brain. Our preliminary studies showed that AZTTP binds to MENPs and the bound drug could be released on demand to almost 100% by AC triggering (magneto-electric field with a 65 Oe magnitude at a frequency of less than 100 Hz).

The above figure is, exaggerated illustration of the concept of on-demand drug release by MENP with an alternating magnetic field: (a) At zero field, only the ionic charge is present in the MENP shell; (b) An additional dipole moment (proportional to the magnetic field) breaks the original symmetry of the charge distribution in the shell; (c) As the field is increased above the threshold value (Qionic ~ QME), the bond on one side is broken. (d) and (e) The field needs to be reversed to break the bond on the side of the nanoparticle. The red arrows show the electric dipole due to the ME effect.