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oai:docta.ucm.es:20.500.14352/921762024-06-28T13:32:57Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Fraguas Sánchez, Ana Isabel author Fernández Carballido, Ana María author Delie, F. author Cohen, M. author Martín Sabroso, Cristina author Mezzanzanica, D. author Figini, M. author Satta, A. author Torres Suárez, Ana Isabel author 2020-07-17 In this work, we evaluated, for the first time, the antitumor effect of cannabidiol (CBD) as monotherapy and in combination with conventional chemotherapeutics in ovarian cancer and developed PLGA-microparticles as CBD carriers to optimize its anticancer activity. Spherical microparticles, with a mean particle size around 25 µm and high entrapment efficiency were obtained. Microparticles elaborated with a CBD:polymer ratio of 10:100 were selected due to the most suitable release profile with a zero-order CBD release (14.13 ± 0.17 μg/day/10 mg Mps) for 40 days. The single administration of this formulation showed an in vitro extended antitumor activity for at least 10 days and an in ovo antitumor efficacy comparable to that of CBD in solution after daily topical administration (≈1.5-fold reduction in tumor growth vs control). The use of CBD in combination with paclitaxel (PTX) was really effective. The best treatment schedule was the pre + co-administration of CBD (10 µM) with PTX. Using this protocol, the single administration of microparticles was even more effective than the daily administration of CBD in solution, achieving a ≈10- and 8- fold reduction in PTX IC50 respectively. This protocol was also effective in ovo. While PTX conducted to a 1.5-fold tumor growth inhibition, its combination with both CBD in solution (daily administered) and 10-Mps (single administration) showed a 2-fold decrease. These results show the promising potential of CBD-Mps administered in combination with PTX for ovarian cancer treatment, since it would allow to reduce the administered dose of this antineoplastic drug maintaining the same efficacy and, as a consequence, reducing PTX adverse effects. Fraguas-Sánchez AI, Fernández-Carballido A, Delie F, Cohen M, Martin-Sabroso C, Mezzanzanica D, et al. Enhancing ovarian cancer conventional chemotherapy through the combination with cannabidiol loaded microparticles. European Journal of Pharmaceutics and Biopharmaceutics 2020;154:246–58. https://doi.org/10.1016/j.ejpb.2020.07.008. 0939-6411 10.1016/j.ejpb.2020.07.008 https://hdl.handle.net/20.500.14352/92176 https://doi.org/10.1016/j.ejpb.2020.07.008 Enhancing ovarian cancer conventional chemotherapy through the combination with cannabidiol loaded microparticles