Prolonged cardioprotective effect of pyridostigmine encapsulated in liposomes.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Vidal
Alessandra Teixeira
AT
CiPharma, Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil.
Guimarães
Homero Nogueira
HN
de Paula
Danielle Cristiane Correa
DC
Frezard
Frederic
F
Silva-Barcellos
Neila Márcia
NM
Grabe-Guimarães
Andrea
A
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage; D010316:Particle Size; D011729:Pyridostigmine Bromide / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013566:Sympathomimetics / Q000008:administration & dosage; D013997:Time Factors
D002316:Cardiotonic Agents; D008081:Liposomes; D013566:Sympathomimetics; D011729:Pyridostigmine Bromide; D009638:Norepinephrine