MGMR® Studies

Safety

In an 18 day mouse study, the Medical Grade MOLECULAR REBAR® (MGMR®) group, dosed every three days for a total of 6 MGMR administrations, demonstrated no observed toxicity.

The group receiving traditional “medical grade” CNT expired on Day 1 after a single dose.

Maximum tolerated dose study:

  • MTD = 70 mg/kg
  • The maximum tolerated dose was 180% higher than the dose used in the previous, successful safety study
  • This opens MGMR up for potential use in a 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

Bio Distribution

Bio Distribution In Vivo

Bio Distribution In Vivo

  • MGMR Initial clearance occurs through the kidney
  • Liver hypothesized to be primary source of later clearance
  • After culmination of the 21-day study, 55.3% of MGMR is eliminated via urine and feces

Untargeted MGMR Biodistribution

  • Studies reveal varied uptake by organs, low, medium, high
  • All organs, except bone, demonstrate continued clearance
  • Observations of bone uptake have led us to expand our bone-borne disease application studies

Untargeted MGMR Biodistribution

Bio Distribution In Vitro

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. This repeated success has been demonstrated in human fibroblasts and MCF10A Breast Cancer cells.

Routes of Administration

Routes of Administration

  • Changing routes of administration alters biodistribution
  • SubQ and IM offer lowest liver retention

Drug Delivery

Intracellular Delivery of Peptide

Intracellular Delivery of Peptide

  • KLAKLAK is a pro-apoptotic peptide which is cell membrane impermeable
  • MGMR binds to KLAKLAK with high affinity and transports it across the membrane where it is released triggering apoptosis
Drug Loading

Drug Loading

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.

  • Small molecules may be loaded across the tube’s inner and outer surfaces
  • Covalent or non-covalent binding to the exterior
  • Multiple functionalities available for targeting moiety attachment
Dosing

Dosing

  • Target and direct MGMR to potentially lower size of effective dose and adverse events
  • Loading optimization accomplished by altering the chemistry of the tubes.
Transdermal Drug Delivery

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

Controlled Release

Release Kinetics

Release Kinetics

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

pH Controlled Release

  • Loading and release can be controlled with pH and temperature
  • Increased shelf stability
  • Enables control over unloading event
  • Optimized for different chemistries
Circulation Times

Circulation Times

  • Blood circulatory times can be changed by altering surface chemistry
  • Modifying circulation time allows for control of system absorption
  • Customized chemistry to direct and retain MGMR carrier where desired
Enhanced PK Performance

Enhanced PK Performance

  • Standard of care, doxorubicin, can be enhanced using MGMR-based delivery
  • Increases early plasma availability
  • Doubles the AUC vs. free drug
  • Stabilizes doxorubicin in the liver