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13.
Effect of free and in poly▫$nano$▫-caprolactone) nanoparticles incorporated new_ type 1 17ß-hydroxysteroid dehydrogenase inhibitors on cancer cells
Kocbek, Petra, farmacevtka ...
Development and progression of breast cancer can be caused by increased estradiol activity, which stimulates cell proliferation. Inhibitors of type 1 17?-hydroxysteroid dehydrogenase (17?-HSD) enzyme ...inhibit estradiol biosynthesis and therefore have potential anticancer activity. In this study two new trans-cinnamic acid esters were established as inhibitors of the humanrecombinant type 1 17?-HSD enzyme. Studied compounds are poorly water soluble and have low stability in aqueous medium. Free inhibitors were tested on T-47D cells, which express the target enzyme, but did not exert any biological effect up to 100 ?M. Therefore, novel poly(?-caprolactone) nanoparticles loaded with the inhibitors were formulated and their effects on T-47D cells were investigated. Prepared nanoparticles had regular spherical shape and mean diameters in the range of 130-170 nm, low polydispersity, high zeta potential and entrapment efficiency. Effective uptake of nanoparticles into T-47D breast cancer cells was confirmed, indicating the possibility to deliver incorporated inhibitor into the cell cytoplasm, where it is released and inhibits the target enzyme. Furthermore, the effect of delivered inhibitors resulted in reduced cell viability and changes in cell morphology. It is anticipated that engineering of efficient delivery system for new poorlysoluble inhibitors led to a significant improvement of their biological activity and stability.
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