Biological evaluation of pyrazinamide liposomes for treatment of Mycobacterium tuberculosis.

Pyrazinamide liposomes were prepared employing the phospholipid molar ratios; dipalmitoyl phosphatidyl choline (7):cholesterol (2) neutral and dipalmitoyl phosphatidyl choline (7):cholesterol (2):dicetyl phosphate (1) negatively charged. Swelling at 52 degrees C led to higher trapping efficiencies. An optimum sterilizing dose of 25 kGy was exhibited by gamma (gamma)-irradiation. Neutral pyrazinamide liposomes (7:2), swollen for 24 h, were employed in biological evaluation for treatment of mice infected by Mycobacterium tuberculosis. Liposomal pyrazinamide could effect highly significant reduction in bacterial counts (colony forming units/g lung), 10, 20 and 30 days after the last treatment dose. Histopathological examination of mice lungs showed highest severity of infection in drug-free liposomes (control) group > pyrazinamide liposomes > free pyrazinamide 6 days/week. The results indicate high therapeutic efficacy of pyrazinamide liposomes, injected twice weekly, in treatment of M. tuberculosis in mice.

Free versus liposome-encapsulated lignocaine hydrochloride topical applications.

The influence of encapsulating lignocaine hydrochloride, in a liposomal delivery system on its release from a topical formulation was studied. Liposomes were prepared from a mixture of L-alpha-dipalmitoylphosphatidyl choline (DPPC) and cholesterol in different molar ratios with or without charge inducing agents. The swelling time affording maximum entrapment was tested from 0-48 h at 53 degrees C. The percentage of drug entrapped in liposomes was found to be charge dependent and more pronounced for negatively charged liposomes. The amount of drug entrapped increased by increasing the ratio of cholesterol. The selected formulations were evaluated in vivo using the pin prick method. The results revealed localized and prolonged activity of lignocaine contained in liposomes when compared with an equivalent conventional topical application.

Free versus liposome-entrapped streptomycin sulfate in treatment of infections caused by Salmonella enteritidis.

Streptomycin sulfate liposomes were prepared by the vortex dispersion method. The liposomes were formulated from a mixture of L-alpha-dipalmitoyl phosphatidyl choline (DPPC), cholesterol with or without (neutral) a charge inducing agent. Two phospholipid molar ratios were considered, namely, DPPC cholesterol 7:2 and 7:4. The amount of streptomycin sulfate entrapped was estimated, microbiologically, and found to range from 0.080 to 1.323% of the initial amount of drug used for preparation of liposomes, depending on the surface charge of the liposomal vesicles. Particle size analysis, measured by the coulter counter, showed a mean particle diameter ranging from 4.417-8.424 microns. Drug targeting experiments were done using Swiss mice as the experimental animals. The in-vivo results indicated that the streptomycin sulfate concentration targeted to the liver and spleen by the liposome encapsulated drug was 2-3 times that exhibited by the free drug. This effect occurred after one day of liposome injection, but it decreased over time from one to seven days. The amount of streptomycin sulfate targeted to the lung, by the liposome formulation 7:2:1 was more than that exhibited by the free drug. This is true only after 7 d from injection. On the other hand, the liposomes of molar ratio 7:4:1 showed much less effect even when compared to the free drug. The survival rate experiments indicated a definite protection against Salmonella enteritidis, exhibited by the liposome-encapsulated streptomycin compared to the free drug.