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oai:docta.ucm.es:20.500.14352/1345002026-04-08T23:51:51Zcom_20.500.14352_14col_20.500.14352_16

Cannabidiol-loaded-injectable depot formulation for the treatment of triple-negative breast cancer: design, development, in-vitro and in-ovo evaluation of its anticancer activity Lozza, Irene Hurtado-Marcos, Carolina Montejo-Rubio, Consuelo Martín Sabroso, Cristina Fraguas Sánchez, Ana Isabel Torres Suárez, Ana Isabel 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. 2026-04-08T13:21:01Z 2026-04-08T13:21:01Z 2026-04-08T13:21:01Z 2026 journal article https://hdl.handle.net/20.500.14352/134500 0378-5173 10.1016/j.ijpharm.2025.125710 eng info:eu-repo/grantAgreement/UCM//FEI 19%2F3001 info:eu-repo/grantAgreement/UCM//FEI 21%2F42 info:eu-repo/grantAgreement/UCM//UCM-910939 Lozza I, Martín-Sabroso C, Hurtado-Marcos C, et al. Cannabidiol-loaded-injectable depot formulation for the treatment of triple-negative breast cancer: design, development, in-vitro and in-ovo evaluation of its anticancer activity. International Journal of Pharmaceutics 2025;678:125710. https://doi.org/10.1016/j.ijpharm.2025.125710 http://creativecommons.org/licenses/by-nc/4.0/ open access Attribution-NonCommercial 4.0 International Elsevier