“Triple-negative breast cancer (TNBC) is an invasive and difficult-to-treat carcinoma that represents 15-20 % of breast malignancies and is frequently diagnosed in younger women. Chemotherapy is the mainstay treatment approach.

Cannabidiol (CBD), the main non-psychoactive cannabinoid, has shown a potential anticancer activity in TNBC, enhancing the effect of conventional antineoplastics.

This research aims to develop in situ forming implants (ISFIs) as a long-acting depot formulation of CBD with potential application in TNBC. This formulation is intended to be administered in the tumor site during neoadjuvant chemotherapeutic regimens, allowing a controlled CBD release. ISFIs were elaborated with 100 mg of polycaprolactone (PCL) and 2.5 mg (2.5-CB-ISFI), 5 mg (5-CB-ISFI) or 10 mg (10-CB-ISFI) of CBD dissolved in 400 µL of NMP. All the formulations exhibited a controlled drug release for around two months. 10-CB-ISFI formulation with the highest CBD content and the most suitable CBD release profile was selected for biological studies.

This formulation inhibited the proliferation and migration of MDA-MB-231 and 4T1 cells and exerted an antiangiogenic effect in ovo. Interestingly, the antiangiogenic activity of 10-CB-ISFI was higher compared with CBD in solution administered at the same concentration, showing vascular inhibition percentages of around 80 % and 60 %, respectively.

Finally, this formulation reduced the growth of MDA-MB-231-derived tumors developed in the chorioallantoic membrane (CAM) model. The single administration of 10-CB-ISFI exhibited a similar antitumor efficacy to the daily administration of CBD in solution (≈60 % tumor growth inhibition).

Therefore, the injectable depot formulation of CBD developed in this work showed a promising utility in TNBC treatment.”

https://pubmed.ncbi.nlm.nih.gov/40349999/

https://www.sciencedirect.com/science/article/pii/S0378517325005472?via%3Dihub