INTRACELLULAR TARGETING OF ANTIBIOTICS BY MEANS OF BIODEGRADABLE NANOPARTICLES

Conditions for attachment of ampicillin to nanoparticles were studied. Drug-release in fetal calf serum was gradual and of zero order, due p robably to the progressive bioerosion of the polymer by the esterases of the serum. Entrapment of ampicillin into nanoparticles was found to improve dramatically the therapeutic efficiency of drug in experiment al intracellular infections of the mouse. On Salmonealla typhimurium i nfected mice, 0.8 mg of ampicillin bound to nanoparticles had a greate r therapeutic effect than 48 mg of free ampicillin. With experimental Listeria monocytogenes infection, the therapeutic index of ampicillin for liver bacterial counts rose at least 20-fold after its leakage to nanoparticles. These results were correlated with the tissue distribut ion profile of ampicillin, which concentrated mainly in the liver and the spleen, the primary foci of infection in the experimental models u sed. The present findings warrant further development of intracellular targeting of kantibiotics with non-liposomal polymeric carriers.