Pyridoclax-loaded nanoemulsion for enhanced anticancer effect on ovarian cancer

Background

Pyridoclax is an original lead, recently identified as very promising in treatment of chemoresistant ovarian cancers. To correct the unfavorable intrinsic physico-chemical properties of this BCS II drug, a formulation strategy was implied in the drug discovery step. Pyridoclax-loaded nanoemulsions (NEs) were developed to permit its preclinical evaluation.

Results

The resulting nanoemulsions displayed a mean size of about 100 nm and a high encapsulation efficiency (>95%) at a drug loading of 2 wt%, enabling a 1,000-fold increase of the Pyridoclax apparent solubility. NEs have enabled a sustained release of the drug as assayed by a dialysis bag method. In addition, anti-tumor effects of the Pyridoclax-loaded nanoemulsions (PNEs) showed a 2.5-fold higher activity on chemoresistant ovarian cancer cells than free Pyridoclax. This effect was confirmed by a drastic increase of caspase 3/7 activation from 10 µM PNEs, as newly objectified by real time apoptose imaging. The Pyridoclax bioavailability was kept unchanged after encapsulation in nanoemulsions as determined in a mice model after oral administration.

Conclusion

Thus, NEs should permit valuable Pyridoclax oral administration, and valorization of this promising anticancer drug by maintaining its original anticancer activity, and by reducing the Pyridoclax therapeutic concentration.

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Article Information: A. C. Groo, S. Hedir, M. Since, E. Brotin, L.-B. Weiswald, H. Paysant, G. Nee, M. Coolzaet,  D. Goux, R. Delépée, T. Freret, L. Poulain, A.S. Voisin-Chiret, A. Malzert-Fréon; International Journal of Pharmaceutics, 2020.