Tuftsin-bearing liposomes as rifampin vehicles in treatment of tuberculosis in mice

Abstract

The antitubercular activity of rifampin was considerably increased when it was encapsulated in egg phosphatidylcholine liposomes. A further increase in the activity was observed when the macrophage activator tetrapeptide tuftsin was grafted on the surface of the drug-loaded liposomes. Intermittent treatments (twice weekly) with these preparations were significantly more effective than the continuous treatments. Rifampin delivered twice weekly for 2 weeks in tuftsin-bearing liposomes was at least 2,000 times more effective than the free drug in lowering the load of lung bacilli in infected animals. However, pretreatment with drug-free tuftsin-bearing liposomes did not render the pretreated animals resistant to the Mycobacterium tuberculosis infections, neither did it appreciably increase the chemotherapeutic efficacy of the liposomized rifampin. These results clearly demonstrate that liposome targeting to macrophages could considerably increase the antitubercular activity of liposomized drugs such as rifampin. Also, it shows that immunoprophylactic treatment with macrophage activators such as tuftsin does not afford any advantage in treatment of tuberculosis infections,

Exploring the Use of Lipid Based Nano-Formulations for the Management of Tuberculosis

“…Intermittent treatments (twice weekly) with tetrapeptide tuftsin grafted rifampin liposomes were found to be 2000 times more effective than free drugs in lowering the lung bacilli load in infected mice. Thus homing of tuftsin grafted liposomes to macrophages may considerably improve the therapeutic efficacy of the liposomized rifampin [38]. Rifabutin (RFB) encapsulated liposomes exhibited lower bacterial loads in the spleen and liver while comparing with free RFB in an in TB-infected mice model.…”

Nanosized Drug Delivery Vectors and the Reticuloendothelial System

“…In mice, targeting of phosphatidylserine liposomes to liver Kupffer cells occurs without the need for prior opsonisation by plasma components (Liu and Liu 1996). However, Agarwal et al (1994) in other species, prior opsonisation is often required to optimize uptake of liposomes by Kupffer cells, highlighting a species difference in the mechanism of macrophage targeting. Similarly, after subcutaneous injection of phosphatidylserine containing liposomes into rats the retention of the lymphatically available dose in regional lymph nodes is over 300% of the injected dose per gram, approximately three-fold higher than subcutaneous administration of phosphatidylcholine or phosphatidylglycerol based liposomes (Oussoren and Storm 1997).…”

Bacteriostatic activity and decomposition products of rifampicin in aqueous solution and liposomal composition

“…Various colloidal compositions of RF, including liposomal ones, have been developed to reduce its toxicity [2 -4]. The antimicrobial activity of the RF liposomal composition in vivo has been demonstrated several times to be more effective than its aqueous solution [5,6]. However, the stability of this RF drug on storage has not been investigated.…”