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:

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

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

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

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

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

PI:  Howard E. Gendelman, MD

Faculty in their own words.

Howard Fox, MD, PhD

Howard E. Gendelman, MD