A novel approach for lung delivery of rifampicin-loaded liposomes in dry powder form for the treatment of tuberculosis

Abstract

Background:Lung administration of antibiotics by nebulization is promising for improved treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, lipid particulate system may improve lung delivery.Materials and Methods:We investigated rifampicin-loaded freeze-dried liposomes. Various formulations were prepared with different drug lipid ratios and one formulation was optimized. Optimized colloidal liposome formulation was freeze-dried and subsequently subjected for various evaluation and characterization parameters such as in-vitro dissolution, in-vitro antitubercular activity, aerodynamic characters, surface morphology, and thermal behavior. The optimized formulation of rifampicin-loaded freeze-dried liposome and free rifampicin was subjected for the in-vivo drug disposition study in Wister rat model by intra-tracheal instillation in comparison with an oral route of administration.Results:The results of pharmacokinetic study for both free drug and the formulation suggested that liposomes released the drug in a controlled manner for a longer period of time. The enhanced efficiency of drug incorporated into liposomes suggested that the delivery of encapsulated drugs to macrophages was more rapid than that of free drug.Conclusion:Therefore, the pharmacokinetic and drug disposition studies provided a sound basis for predicting the successful treatment for tuberculosis.

Co-encapsulation of Rifampicin and Isoniazid in Crude Soybean Lecithin Liposomes

“…Patil et al 39 observed a decrease in the rate of RIF release as cholesterol content increased, whereas in these studies no major difference was observed in the kinetics of RIF release for the liposome formulations tested (Fig. 5).…”

“…This is consistent with the observation reported elsewhere and suggests that RIF is getting amorphous in liposomes. 39,44 The probable explanation should be the fact that RIF's molecules are deeply embedded into the lipid bilayers as suggested by Rodrigues et al 40…”

“…The same phenomenon was previously observed when RIF was encapsulated alone using phosphatidyl choline from soybean lecithin. 39 This could be due to potential saturation of the liposomal membranes when RIF and cholesterol are used simultaneously, as both compounds are lipophilic and tend to preferentially locate in lipid bilayers. 18,40 This saturation may also have affected INH loading during the freeze-thawing process, which relies on diffusion of INH molecules to into liposomal vesicles.…”

“…This confirms the loss of crystallinity of RIF in liposomes revealed by DSC and previously reported in the literature. 39,44…”

Epidemiology of Tuberculosis and Drug Resistance in Tuberculosis Treatment in Indian Patients

“…MTB may have killed more persons than any other microbial pathogen. The inadequacy of awareness and treatment results in major health problems, where the results are complicated [1][2][3][4].…”