Kanamycin incorporation in lipid vesicles prepared by ethanol injection designed for tuberculosis treatment

The primary goal of this study was the production of liposomes encapsulating kanamycin for drug administration by inhalation. The selected drug is indicated for multiresistant tuberculosis, and administration through inhalation allows both local delivery of the drug to the lungs and systemic therapy. The ethanol injection method used for the liposome production is easily scaled up and is characterized by simplicity and low cost. Vesicles were prepared using different lipid compositions, including hydrogenated soybean phosphatidylcholine and cholesterol (SPC/Chol), egg phosphatidylcholine and cholesterol (EPC/Chol), distearoyl phosphatidylcholine and cholesterol (DSPC/Chol), distearoyl phosphatidylcholine, dimyristoyl phosphatidylethanolamine and cholesterol (DSPC/DMPE/Chol), dipalmitoyl phosphatidylcholine and cholesterol (DPPC/Chol) and dipalmitoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol and cholesterol (DPPC/DPPG/Chol). The effects of different operational conditions for vesicle production and drug encapsulation were evaluated, aiming at a compromise between final process cost and suitable vesicle characteristics. The best performance concerning drug incorporation was achieved with the DSPC/Chol system, although its production cost was considerably larger than that of the natural lipids formulations. Encapsulation efficiencies up to 63% and final drug to lipid molar ratios up to 0.1 were obtained for SPC/Chol vesicles presenting mean diameters of 132 nm incubated at 60 degrees C with the drug for 60 min at an initial drug-to-lipid molar ratio of 0.16.