Efficacy of Combined Rifampicin Formulations Delivered by the Pulmonary Route to Treat Tuberculosis in the Guinea Pig Model

Abstract

Liposomes, as vehicles alone or in combination with rifampicin (RIF) microparticles (RMs), were evaluated as vehicles to enhance the permeation of RIF into granulomas. RIF liposomes (RLs) were extruded through a 0.1 µm polypropylene membrane. RMs were prepared by the solvent evaporation method. Four weeks after infection, guinea pigs (GPs) were assigned to groups treated with a combination of RM-RLs or RLs alone. RLs were nebulized after extrusion whereas RMs were suspended in saline and nebulized to GPs in a nose-only inhalation chamber. Necropsy was performed after the treatment; the lungs and spleen were resected for bacteriology. RLs had mean diameters of 137.1 ± 33.7 nm whereas RMs had a projected area diameter of 2.48 µm. The volume diameter of RMs was 64 ± 1 µm, indicating that RMs were aggregated. The treatment of TB-infected GPs with RLs significantly reduced their lung bacterial burden and wet spleen weight compared with those treated with blank liposomes. The treatment of TB-infected animals with RM-RLs also reduced their lung bacterial burden and wet spleen weight even though these reductions were not statistically different. Based on these results, the permeation of RIF into granulomas appears to be enhanced when encapsulated into liposomes delivered by the pulmonary route.

The Pharmacokinetics of CPZEN-45, a Novel Anti-Tuberculosis Drug, in Guinea Pigs

“…A comparison of each treatment was performed using a non-parametric ANOVA (Kruskal–Wallis test) with Dunnett’s multiple comparison test to determine which experimental groups were significantly different from each other. The p -values for the primary analysis and the adjusted p -values for the multiple comparisons <0.05 were considered statistically significant [ 21 ].…”

Breaking barriers: The potential of nanosystems in antituberculosis therapy

“…This enhancement indicates their potential as nanocarriers for poorly soluble anti-TB drugs. [ 257 ] RIF-loaded Liposomes 137 N/A In this study, the guinea pigs were exposed to an inhalation dose of 2.83 mg/kg Significant reduction in inflammation levels, inferred from the organ weights, and a decreased bacterial load in the lung regions of the guinea pigs, suggesting that the nanocarrier enhances granulomatous penetration [ 258 ] Hydrophilic Streptomycin Sulfate SLNs (STRS-SLN) 218.1 Enhanced intracellular absorption in THP-1, LoVo, and DLD-1 cells. 3-fold MIC reduction against MTB H37RV compared to free STRS Wistar rats, oral administration 90 mg/kg STRS-SLN plasma concentration surpassed the STRS group.…”

“…García-Contreras et al [ 285 ] developed two systems: RIF-loaded liposomes (comprising L-α-phosphatidylcholine and cholesterol) and RIF-loaded PLGA microparticles (by the emulsion/solvent evaporation method). They individually assessed the penetration capabilities of both nanosystems into granulomas.…”

“…7 A) Wet organ weights of animals infected with tb based on the treatment, B) Number of viable bacteria in the lung and spleen tissues of the animals at necropsy after 10 days of treatment. RIF-loaded microparticles (RM); RIF-loaded liposomes (RL); RM-RL association; control for microparticles and liposomes (BL-BM) [ 285 ]. Reprint published from open access article by MDPI Copyright 2021.…”

Advanced drug delivery and therapeutic strategies for tuberculosis treatment

“…Pulmonary TB is the most common form of TB, and inhalable carriers of ATDs have been a major focus of research and were found to significantly increase targeting in the lungs, reducing undesirable toxic side effects and enabling delivery to AM [9,14]. Liposomes [261], microparticles [186,187,262], microencapsulation [80], liquid crystals [263], hydrogels [244], polymeric micelles [96] and even hybrid systems [264] have been promising for inhalational TB therapy. The formulations need to be optimized to penetrate mucous layers and biofilms and overcome sequestration, rapid deactivation by enzymes, and elimination by coughing [265,266].…”