Prolonged cardioprotective effect of pyridostigmine encapsulated in liposomes.

Aims: The purpose of the present work was to investigate the ability of pyridostigmine encapsulated in long-circulating liposomes, to protect against ECG (electrocardiogram) alterations induced by sympathetic stimulation in rats.

Main Methods: The encapsulation of pyridostigmine was carried out by freeze-thaw and extrusion. Blood pressure and ECG (limb lead II) were monitored in anaesthetized male Wistar rats. The formulation containing pyridostigmine was intravenously administrated in 0.1, 0.3 and 1.0mg/kg doses, and sympathetic stimulation was conducted by administration of 1 or 3 microg of noradrenaline (NA) after 1, 2, 4 or 6h. The obtained cardiovascular parameters were compared to animals that received intravenous injection of pyridostigmine in free form or saline.

Key Findings: After saline, NA induced a significant increase in QT interval (22.3% after 3.0 microg). Previous administration of free pyridostigmine significantly prevented the increase of QT interval after sympathetic stimulation and the most prominent effect was observed after 1h for the dose of 0.3mg/kg (6.8% after 3.0 microg of NA) and was no longer observed after 2h of the treatment. On the other hand, the maximum effect of pyridostigmine in liposomal formulation preventing QT interval increase was observed 2h after treatment (9.7% after 3.0 microg of NA) and was still present until 6h when 1mg/kg was previous administrated.

Significance: The results of the present study, beyond to confirm the cardioprotective action of pyridostigmine, suggest that liposomal pyridostigmine may be a potential therapeutic alternative to prevent cardiovascular disturbances resulting from sympathetic hyperactivity.