To ensure efficacy, conventional antiretroviral therapies (ART) require frequent administration to maintain plasma and tissue drug concentrations in the therapeutic range. ART’s failure to eliminate HIV-1 at sites of restricted infection underpins its limitations. ART’s half-life, tissue biodistribution and maintenance of optimal therapeutic drug levels at anatomical sites could be realized through cell and tissue targeted long acting slow effective delivery systems and by optimizing drug metabolism. My research interests are in the areas of design, development and evaluation of antiretroviral prodrugs, development of long acting slow effective release ART (LASER ART) and their application to testing in cell and small animal based assays. In collaboration with Dr. Howard Gendelman and members of the nanomedicine laboratory at UNMC, we have demonstrated that both hydrophilic and hydrophobic therapeutic compounds could be converted into LASER ART. Single administration of LASER ART significantly extends the half-life of therapeutic compounds. The LASER ART are developed through novel chemistry strategies coupled with autophagy stimulation to sustain cell and tissue ART depots.

One of our research goals is to translate existing antiretroviral drugs (ARVs) into long acting compounds. We are focused on making a library of LASER ART targeting multiple phases of the viral life cycle to limit viral resistance while improving patient compliance. ARVs are first converted into hydrophobic and lipophilic prodrug nanocrystals for efficient transfer across cell and tissue barriers. Targeting ligands are covalently linked to the surface of LASER ART particles to facilitate entry into cell and tissue reservoirs of infection. LASER ART maximizes drug-loading capacity by holding excipient content to a minimum. A range of immune and intracellular LASER ART depot boosters serve to enhance viral clearance. The ultimate goal of this work is to make LASER ART regimen with once-monthly or longer dosing intervals for treatment and prevention of HIV-1.

Another area of interest is the development of theranostic nanoparticles for rapid screening of targeting ligands and non-invasive assessment of LASER ART biodistribution by magnetic resonance imaging (MRI).LASER ART and theranostic nanoparticle sizes are in the same range and both encapsulate hydrophobic and lipophilic ART compounds.