NanoART Manufacture, Delivery and Pharmacokinetics

This is an integrative cross approach translational and multi-investigator program grant seeking to develop nanoformulated antiretroviral drug therapy from the bench to the patient.

The grant consists of three project supported by three cores:

• Project 1: Nanoformulation Manufacture and Characterization
• Project 2: Nanoformulation Uptake, Release, Toxicology and Tissue Delivery
• Project 3: Nanotherapeutics for Lentivirus Infected Rodents and Monkeys
• Core A: Administrative
• Core B: Bioimaging
• Core C: Pharmacokinetics and Drug-Drug Interactions

Publications resulting from this grant.

Project 1: Nanoformulation Manufacture and Characterization will

• manufacture and characterize stable and safe nanosuspension dosage forms of antiretroviral drugs
• develop polymeric micelles for delivery of antiretroviral drugs

Project 2: Nanoformulation Uptake, Release, Toxicology and Tissue Delivery will

• text formulations of nanoART including EFV, RTV, IDV, ATV, and LPV
• conduct in-depth pharmacokinetic profiles of the "go" formulations

Howard E. Gendelman, MD
402-559-8920
hegendel@unmc.edu

Project 3: Nanotherapeutics for Lentivirus Infected Rodents and Monkeys will

• examine the efficacy of selected nanoART formulations in two mouse models of HIV infection
• examine the hypothesis that nanoART formulations exhibit a prolonged useful half-life in the plasma of primates

Howard S. Fox, MD, PhD
402-559-4810
hfox@unmc.edu

Core A: Administrative will

• coordinate the interdisciplinary relationships among the projects and core B and C
• provide research direction, statistical and advisory support

Howard E. Gendelman, MD
402-559-8920
hegendel@unmc.edu

Core B: Imaging will

• use MRI and SPECT/CT methods to measure the nanoART biodistribution and tissue uptake kinetics with histological validation at the experimental endpoint
• use ¹H MRS, diffusion tensor imaging and blood-brain barrier permeability to track effects of viral-associated neurodegeneration and efficacy of nanoformulations

Mike Boska, PhD
402-559-3138
mboska@unmc.edu

Core C: Pharmacokinetics and Drug-Drug Interactions will

• develop high performance liquid chromatography-tandem mass spectrometry methods to simultaneously quantify all five antiretrovirals in humans cells and mice and monkey plasma, tissues and fluids  including brain, liver, spleen, lymph nodes, lung and CSF
• analyze and interpret the pharmacokinetic data generated from the preclinical studies in Project 2 and Project 3

Courtney Fletcher, PharmD
402-559-1962
cfletcher@unmc.edu