Incorporation of Antibiotics in Liposomes Designed for Tuberculosis Therapy by Inhalation

Abstract

Liposomal encapsulation of tuberculostatic drugs can potentially increase their therapeutic index. The incorporation of isoniazid, pyrazinamide, rifampicin, ethionamide, and streptomycin in extruded distearoylphosphatidylcholine/cholesterol liposomes designed for administration through inhalation was evaluated. Ethionamide and rifampicin were incorporated during lipid film formation, whereas solutions of the remaining drugs were used to hydrate preformed lipid bilayers. Final drug to lipid ratios around 0.3 were achieved for isoniazid and pyrazinamide, and mean vesicle diameters varied from 286 to 329 nm. No expressive drug leakage or mean vesicle diameter changes occurred during 3 weeks. No significant incorporation was achieved for streptomycin, ethionamide, and rifampicin.