Drug Delivery

Transient Opening of Permeability Barriers for Drug Delivery

MediLumine has licensed a set of bradykinin receptor modulators developed by scientists at University of Sherbrooke for in vivo and in vitro research. These receptor modulators are available for preclinical research exclusively through MediLumine are based in a proprietary sequence of natural and unnatural amino acids which resist enzymatic degradation, have a superior pharmacokinetic profile and are selective for both animal human versions of the bradykinin receptors.

As a tool for research, bradykinin receptor agonism is used in various in-vivo animal models of disease which involve up-regulation of Bradykinin receptors. For example, the blood-brain barrier (BBB), a powerful physiological barrier that seriously impairs the delivery of various therapeutic compounds to the brain can be transiently opened with agonism of the Bradykinin B2 Receptor. The blood brain tumor barrier can be selectively opened with bradykinin B1R receptor agonism thus increasing delivery of imaging agents and anticancer drugs to the brain tumor.

Expression of Bradykinin B1 receptor is induced in various disease states like pain and cancer. Antagonism of this receptor is well known to have therapeutic indications in various disease states like cancer and pain. Inducible B1R are involved in various models of inflammation, diabetes mellitus and other types of vasculopathies, pain syndromes, cancer, angiogenesis, multiple sclerosis, epilepsy, and Alzheimer disease.


Chemical Opening of Blood Brain Barrier

Representative intravital confocal images of a mouse brain microvasculature following i.v. injection of FITC-Dextran (MW 2 MDa) (A) and 30 min post-injection of MediLumine’s B2R agonist (0.050 mg/kg or 1.25 μg/mouse) showing extrasavation of FITC-Dextran (B). Scale represents the intensity of fluorescence (Courtesy of Drs Martin Lepage and Fernand Gobeil).





  1. Fernandes PD, Gomes N de M, Sirois P. The bradykinin B1 receptor antagonist R-954 inhibits Ehrlich tumor growth in rodents. Peptides. 2011 32: 1849–1854
  2. Kaufman GN, Zaouter C, Valteau B, Sirois P, Moldovan F. Nociceptive tolerance is improved by bradykinin receptor B1 antagonism and joint morphology is protected by both endothelin type A and bradykinin receptor B1 antagonism in a surgical model of osteoarthritis. Arthritis Research & Therapy. 2011;13(3):R76. doi:10.1186/ar3338.
  3. Catanzaro O., Capponi J. A., Michieli J., Labal E., Di Martino I., Sirois P. (2013). Bradykinin B(1) antagonism inhibits oxidative stress and restores Na+K+ ATPase activity in diabetic rat peripheral nervous system. Peptides 44, 100–104. 10.1016/j.peptides.2013.01.019
  4. Catanzaro O, Labal E, Andornino A, Capponi JA, Di Martino I, Sirois P. Blockade of early and late retinal biochemical alterations associated with diabetes development by the selective bradykinin B1 receptor antagonist R-954. Peptides. 2012;34:349–352.
  5. Catanzaro OL, Dziubecki D, Obregon P, et al. Antidiabetic efficacy of bradykinin antagonist R-954 on glucose tolerance test in diabetic type 1 mice. Neuropeptides. 2010;44:187–189.
  6. Vasquez-Pinto L. M., Nantel F., Sirois P., Jancar S. (2010). Bradykinin B(1) receptor antagonist R954 inhibits eosinophil activation/proliferation/migration and increases TGF-beta and VEGF in a murine model of asthma. Neuropeptides 44 107–113

Selective Opening of Blood Brain Tumor Barrier for Drug Delivery and Brain Tumor Imaging

  1. Côté J, Savard M, Neugebauer W, Fortin D, Lepage M, Gobeil F. Dual kinin B1 and B2 receptor activation provides enhanced blood–brain barrier permeability and anticancer drug delivery into brain tumors. Cancer Biology & Therapy. 2013;14(9):806-811.
  2. Côté J, Bovenzi V, Savard M, Dubuc C, Fortier A, et al. (2012) Induction of Selective Blood-Tumor Barrier Permeability and Macromolecular Transport by a Biostable Kinin B1 Receptor Agonist in a Glioma Rat Model. PLoS ONE 7(5): e37485. doi:10.1371/journal.pone.0037485

Safety and Pharmacokinetics

  1. Savard M, Côté J, Tremblay L, Neugebauer W, Regoli D, Gariépy S, Hébert N, Gobeil F. Safety and pharmacokinetics of a kinin B1 receptor peptide agonist produced with different counter-ions.  Biol Chem 397(4): 365-372
  2. Savard M, Côté J, Tremblay L, Neugebauer W, Regoli D, Gariépy S, Hébert N, Gobeil F. Preclinical pharmacology, metabolic stability, pharmacokinetics and toxicology of the peptidic kinin B1 receptor antagonist R-954. Peptides. 2014 Feb;52:82-9. doi: 10.1016/j.peptides.2013.12.009. Epub 2013 Dec 18.