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

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.

Further studies on the hypoxia produced by canatoxin in rats

Canatoxin, a convulsant neurotoxin from the seeds of Canavalia ensiformis, induces lipoxygenase-dependent hypoxia in rats which is blocked by hexamethonium. The purpose of the present study was to examine the relationship between canatoxin-induced hypoxia and bronchoconstriction. Since several effects of the toxin are very similar to those described for morphine and opioid-like peptides, the effects of opioid antagonists were also investigated. Pretreatment of male, adult Wistar rats (200-250 g) with cyproheptadine (80 ug/kg, ip, N=6) and isoproterenol (100 ug/kg, ip, N+6) partially blocked (% variation of pO2:CNTX alone: -26.67 ñ 2.56, N=6; with cyproheptadine: 16.15 ñ 2.97*, N=6; with isoproterenol: 17.73 ñ 1.93*, N=6; *P<0.05 as compared to CNTX alone) the hypoxia but no effect was observed with diphenhydramine (2 mg/kg, ip, N=6) or atrophine (2 mg/kg, ip, N=6). The hypoxemic effect of canatoxin (100 ug/kg iv 20 min, N=6) was also almost completely blocked with either naloxone (1 mg/kg, sc, N=6) or naltrexone (5 mg/kg, sc, N=6). The results presented here provide evidence suggesting that both opioid peptides and bronchoconstriction seem to play a role in the hypoxia caused by canatoxin