APPROACHES TO IMPROVE THE ASSOCIATION OF AMIKACIN SULFATE TO POLY(ALKYLCYANOACRYLATE) NANOPARTICLES

Owing to the low rate of association of polar drugs, such as amikacin sulphate, to hydrophobic carriers, e.g. poly(alkylcyanoacrylate) nanoparticles, several procedures have been investigated to improve the drug carrier capacity. The greatest improvement was noted with the covalent reaction between the drug and the suspension agent dextran 70, attached to the particle surface. The antibacterial activity in this case was dramatically reduced, however. The addition of sodium lauryl sulphate to the polymerisation medium reduced the hydrosolubility of the drug, improving its incorporation into the nanoparticles. The study of the sorption behavior of amikacin sulphate onto freeze-dried nanoparticles, prepared either using a surfactant (Synperonic F 68) or a suspension agent (dextran 70), shows preferrable results in the former case. The presence of drug in the polymerisation medium drastically increased the mean particle size, destabilising the nanoparticles at the highest concentration assayed (20 mg/ml). Less drug was adsorbed onto these particles at a later stage, which seems to be due to their larger size compared to non-loaded nanoparticles. Moreover, the drug-polymer association mechanism, investigated by zeta-potential studies, appears to be an electrostatic interaction, in keeping with the observed reduction of particle surface charge after adsorption of amikacin. Finally, the modification of the polymer molecular weight in the formulations developed was investigated.