SIGNIFICANT ENTRY OF TUBOCURARINE INTO THE BRAIN OF RATS BY ADSORPTION TO POLYSORBATE 80-COATED POLYBUTYLCYANOACRYLATE NANOPARTICLES - AN IN-SITU BRAIN PERFUSION STUDY

The possibility of using polysorbate 80-coated polybutylcyanoacrylate nanoparticles to deliver low molecular polar hydrophilic drugs to the CNS has been studied. Tubocurarine (a quaternary ammonium salt) does n ot penetrate the normal intact blood-brain barrier. However, the injec tion of this drug directly into the cerebral ventricles of the brain p rovokes the development of epileptiform seizures as assessed by electr oencephalogram (EEG). An in situ perfused rat brain technique was used as an experimental technique together with a simultaneous recording o f the EEG. Nanoparticles were prepared by butylcyanoacrylate polymeriz ation in an acidic medium. Fifteen minutes after the introduction of t ubocurarine-loaded polysorbate 80-coated nanoparticles into the perfus ate, epileptiform spikes in the EEG appeared. Intraventricular injecti on of tubocurarine caused the appearance of the EEG seizures 5 min aft er administration. Neither tubocurarine solution nor tubocurarine-load ed nanoparticles without polysorbate 80 or a mixture of polysorbate 80 and tubocurarine were able to influence the EEG. Thus only the loadin g of tubocurarine onto the polysorbate 80-coated nanoparticles appears to enable the transport of this quaternary ammonium compound through the blood-brain barrier.