Frequency domain electrical conductivity measurements of the passive electrical properties of human lymphocytes

Use of liposomes as carriers of gentamicin for intrabronchial pulmonary delivery was investigated in rabbits. Gentamicin, in isotonic glutamic acid buffer, pH 4.5, was encapsulated in multilamellar vesicles (MLVs) and administered intrabronchially. Higher drug concentrations were found at the pulmonary site of liposome instillation for 1 day as compared with free unencapsulated antibiotic. When time-course distributions of gentamicin given in the liposomal or free form were measured in bronchoalveolar lavages (BAL), similar accumulations were observed up to 4 h, but the drug remained longer (24 h) after administration of the liposomal formulation. Higher amounts of antibiotic were detected in BAL supernatant 1 h after instillation of plain gentamicin; this difference stopped being significant after 4 h. A microbiological assay outlined the bacteriostatic activity of gentamicin released from MLVs and recovered in BAL supernatant. Liposomal gentamicin accumulated in the BAL cell pellet 1 h after intrabronchial instillation; it decreased progressively but minute amounts were still detected after 1 day. On the contrary, no gentamicin was found in the pellet at any time after free drug administration. Comparison of aminoglycoside concentrations in plasma and kidneys indicated lower and constant levels when the liposomal form was instilled. Liposome encapsulation altered the disposition of gentamicin in a way suggesting improved pulmonary concentration and lower systemic toxicity.