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.
El-Ridy
M S
MS
Pharmaceutical Technology Department, National Research Centre (NRC), Dokki, Cairo 12622, Egypt.
Mostafa
D M
DM
Shehab
A
A
Nasr
E A
EA
Abd El-Alim
Sameh
S
D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D015169:Colony Count, Microbial; D007279:Injections, Subcutaneous; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000254:growth & development*; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011897:Random Allocation; D014376:Tuberculosis / Q000188:drug therapy* / Q000378:metabolism
D000995:Antitubercular Agents; D008081:Liposomes; D011718:Pyrazinamide