Implants composed of digoxin and poly(ε-caprolactone): development, characterization, anti-proliferative and anti-angiogenic activities.

ABSTRACT

Drug delivery systems could be applied to locally treat cervical cancer, thus preventing the drawbacks of conventional therapy. In this study, anti-proliferative and anti-angiogenic effects of digoxin incorporated into poly(ε-caprolactone) implants were evaluated, aiming at the local treatment of cervical cancer. Implants were characterized, and the in vitro release profile of digoxin was demonstrated. Anti-proliferative and anti-angiogenic activities of digoxin were investigated by using chorioallantoic membrane and human cervix carcinoma (HeLa) cells, respectively. The chemical structure of digoxin and the semi-crystalline nature of poly(ε-caprolactone) were preserved after designing implants. The hydrophobicity of drug and polymer as well as the semi-crystalline structure provided a controlled diffusion of digoxin from implants. Digoxin released from implantable devices exhibited anti-proliferative activity against HeLa cells. The anti-angiogenic effect was also shown. Finally, implants composed of digoxin and poly(ε-caprolactone) could be applied as a therapeutic alternative to treat the early stage of cervical cancer, once they were able to locally control the release of this anti-angiogenic and anti-proliferative drug, minimizing its systemic side effects and toxicity.