MGMR® Studies

Safety

In an 18 day mouse study, the Medical Grade MOLECULAR REBAR®(MGMR®) group were dosed with 6 doses of MGMR, administered every three days, and demonstrated:

  • No toxicity observed
  • No organ accumulation observed
  • Extended circulation in the blood

The group receiving traditional “medical grade” CNTs all expired on Day 1 after one dose.

Maximum tolerated dose study:

  • The maximum tolerated dose was 180% higher than the dose used in the previous, successful safety study

  • The multiple dose (daily) arm of the new study was deemed well tolerated and represented an increase in dose of 60% from the previous study. This was not the maximum tolerated daily dose (the maximum is likely significantly higher), but a representative dose we studied

  • This opens MGMR up for potential use in a very broad range of drug delivery applications – even less potent drugs requiring a higher dose volume

Three transdermal patch studies concluded:

  • No irritation
  • No cell lysis
  • No cytotoxicity

Release Kinetics

  • MGMR has demonstrated sustained release over 7+ days utilizing GRAS recipients
  • Local release can be stimulated with MRI and NIR

Bio Distribution In Vivo

Preliminary study shows there is no accumulation of MGMR in

  • Lung
  • Lymph
  • Brain
  • Heart

Mouse lung from MGMR study (top) demonstrating no residual accumulation versus hyperspectral image of blood (bottom), where MGMR is seen as white and is evenly dispersed.

Bio Distribution In Vitro

MGMR has demonstrated intracellular penetration within minutes. MGMR distributes within the cell and naturally localizes in the nucleus, nucleoli, and the actin cytoskeleton

Active Targeting Ex Vivo

MGMR can be preferentially targeted to the bone

  • Using Fluorescent Microscopy, the bright signal observed confirms MGMR targeting the bone

Transdermal Drug Delivery

MGMR was fully dispersed and polymerized into an ultrathin (1 to 5 microns) polymer-sheet, then coated onto a membrane support. Holes cut in the membrane support allow for the visualization of the ultrathin transparent membrane loaded with fully dispersed MGMR.

  • Free MGMR (not loaded) and MGMR filled with drug in ultrathin film have been dispersed
  • In three transdermal patch studies, MGMR was applied with no irritation, contact sensitization, cell lysis, or cytotoxicity observed

Drug Loading

Large molecules (e.g., proteins, peptides, antibodies) can be either covalently or non-covalently bonded to the exterior of MGMR and smaller molecules (<10,000 daltons) can be loaded inside MGMR. Successful research performed to-date demonstrating loading and bonding of multiple substances within or onto MGMR includes:

  • Loaded insulin, chlorambucil, and bortezomib to the inside of MGMR
  • An enzyme and large molecule, horseradish peroxidase (HRP), was attached to the outer surface of MGMR both covalently and non-covalently. HRP remained strongly bound and retained function
  • Undecapeptide, QSYQAKANNYC, was attached to MGMR and labeled with tetramethyl rhodamine iodoacetamide. This peptide labeled MGMR was readily taken up by a variety of cell lines with no observed cytotoxicity. Many anti- angiogenic peptides are of similar length
  • Alendronate and Cy5 dye were covalently attached to the surface of MGMR using a standard bifunctional cross-linker. Fluorescence was observed, and bone targeting was successful. Both small molecules retained their function
  • Simultaneously loaded small dextran polymers and small molecule dyes into MGMR. The addition of the dextran polymer caused the release of the dye to occur over a longer period of time, demonstrating that both molecules were loaded into the interior of the MGMR and resulted in a method for controlled and sustained release