Disposition of liposomal gentamicin following intrabronchial administration in rabbits.

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.

An automated micromethod for detection of lytic antimycobacterial antibodies by immune lysis of liposomes sensitized to tuberculin.

Calcein was concentrated inside multilamellar liposomes (MLV) by encapsulation through an osmotic gradient in order to increase its quenching. Immune lysis of these MLV sensitized to PPD by direct encapsulation or by exposure to preformed vesicles was studied in the presence of rabbit anti-BCG serum and of a non-immune rabbit serum as a source of complement, successively added in the wells of a microplate to a final volume of 0.1 ml. A 40 to 50% release of encapsulated calcein was observed after 5 min using a Titertek Fluoroskan II. Preformed liposomes exposed to PPD were more sensitive to anti-BCG serum than liposomes formed in PPD. Trials with human sera revealed a significantly higher level of specific lytic immunoglobulins in tuberculous patients than in non-tuberculous subjects. Key words: Liposome immune lysis assay; lytic antimycobacterial antibodies; tuberculosis, human; test automation.