Cannabidiol Loaded Nanoparticles Exhibit an Anti-Fibrotic Effect in a Mouse Model of Non-Ischemic Heart Failure

Introduction: Cannabidiol (CBD) is being studied in a spectrum of ailments including cardiovascular disorders. It is also clinically prescribed for certain diseases. However, the hydrophobicity of CBD has been reported to contribute to low oral bioavailability. Here we use a polymeric nanoparticle formulation of CBD (nCBD) to overcome this limitation and evaluate its potential in heart failure (HF). Methods: HF was induced in 3-month old C57BL/6J mice with drinking water containing 1% NaCl and 0.3 mg/mL of L-NAME. After 1-week, subcutaneous osmotic pumps were implanted to deliver angiotensin-II at a rate of 0.7mg/kg/day for 4 weeks. nCBD was prepared using co-solvent evaporation of poly(ethylene oxide)-poly(α-benzyl carboxylate-ε-caprolactone) (PEO-b-PBCL) and pharmaceutical-grade CBD. nCBD (1 mg/kg) was injected 2 times per week subcutaneously in HF mice and Control mice. At week 5, Masson’s trichrome and H & E staining was performed to evaluate severity of fibrosis and cardiomyocyte (CM) size respectively using Cell Sense Dimension Software from Olympus. Results: PEO-b-PBCL nanoparticles localized in both interstitial and replacement fibrotic regions in the heart of our HF mice. HF mice with nCBD treatment displayed less fibrosis when compared to HF mice without treatment as shown in a representative image of fibrosis staining (Figure A). Histological quantification depicted that fibrosis area was higher in HF mice and was significantly (p<0.0001) reduced in HF mice exposed to nCBD (Figure B). Treatment of HF mice with nCBD also influenced CM size. Normal mice had a mean CM size of 12.33±2.07 μm. This increased to 21.17±2.88 μm in HF mice without treatment. However, nCBD treatment significantly (p<0.0001) decreased CM size to a mean value 14.76±2.71 μm (Figure C). Conclusion: Our results show that nCBD has an anti-fibrotic and anti-hypertrophic effect in a mouse model of non-ischemic heart failure.