Enhanced intramacrophage activity of resorcinomycin A against Mycobacterium avium-Mycobacterium intracellulare complex after liposome encapsulation

Abstract

The activities of free and liposomal resorcinomycin A against Mycobacterium avium-Mycobacterium intracellulare complex (MAC) grown in broth and in murine peritoneal macrophages were evaluated. Liposomal resorcinomycin A was composed of dimyristoyl phosphatidylcholine and phosphatidylinositol at a molar ratio of 9:1. Both free resorcinomycin A and liposomal resorcinomycin A showed no toxicity to macrophages at concentrations up to 50 micrograms/ml, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Minimal inhibitory concentrations of free resorcinomycin A and liposomal resorcinomycin A in broth were 6 and 12 micrograms/ml, respectively, as determined by the MTT colorimetric microassay. In macrophages, liposomal resorcinomycin A caused significantly higher intramacrophage antimycobacterial activity than the free form of the drug. At doses ranging from 6 to 50 micrograms/ml, liposomal resorcinomycin A caused 50 to 93% MAC growth inhibition, respectively (as determined by CFU), while free resorcinomycin A was associated with 33 to 62% MAC growth inhibition, respectively, 3 days after drug treatment. In addition, antimycobacterial activity of liposomal resorcinomycin A in macrophages was maintained 7 days after treatment, whereas the activity of free resorcinomycin A was reduced to negligible 3 days after treatment. In summary, liposome encapsulation of resorcinomycin A resulted in significant enhancement of antibacterial activity against intramacrophagic MAC infection.

The challenges and applications of nanotechnology against bacterial resistance

“…The -Flores et al, 1996;Onyeji et al, 1994aOnyeji et al, , 1994bOnyeji et al, 1995). Additionally, Faria and…”

“…The NPs have an advantage of releasing persistently and tardily in the intracellular targeted location. The process of biodegradable NPs-drugs in the intracellular is dynamic and complicated, including intracellular trafficking, endocytosis, releasing, and -Flores et al, 1996;Onyeji et al, 1994aOnyeji et al, , 1994bOnyeji et al, 1995). Additionally, Faria and Roman reported that the PLGA loading isoniazid analog could increase the drug concentrations located inside of the macrophages to kill the Mycobacterium tuberculosis (de Faria et al, 2012).…”

“…The NPs materials included in liposomes, poly (butyl cyanoacrylate), Poly (isobutyl cyanoacrylate), PLGA (Poly, D, L‐lactide‐co‐glycolide) loading drugs have been reported on intracellular uptake in a number of previously published studies. Onyeji, Nightingale, Gomez et al reported that the liposome loading charithromycin, olfoxacin, azithromycin, rifabutin, and clarithromycin could enhance the cellular uptake and increase the activities of agents (Gomez‐Flores et al., 1996; Onyeji et al., 1994a, 1994b; Onyeji et al., 1995). Additionally, Faria and Roman reported that the PLGA loading isoniazid analog could increase the drug concentrations located inside of the macrophages to kill the Mycobacterium tuberculosis (de Faria et al., 2012).…”

Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

“…Examples include, but are not limited to, novel drug delivery systems, as is the case of nebulized liposomes for pulmonary targeting [ 26 , 42 , 43 , 48 , 66 , 67 , 68 , 69 ], nano-formulations and polymeric particles [ 64 , 70 , 71 ], and chemical compounds restoring antimicrobial susceptibility, among which efflux pump inhibitors deserve to be mentioned [ 72 , 73 ].…”

Toward an Optimized Treatment of Intracellular Bacterial Infections: Input of Nanoparticulate Drug Delivery Systems

“…Monocytes, macrophages Gentamicin 1990 [79] Monocyte-derived macrophages Streptomycin 1992 [80] Murine J 774 cells Azithromycin, rifabutin, clarithromycin 1994 [81] Rifampicin 2009 [82] Human blood-derived macrophages Sparfloxacin 1996 [83] Human macrophages Ciprofloxacin and azithromycin 1995 [84] Ofloxacin; clarithromycin 1994 [48] Murine peritoneal macrophages Granulocyte-macrophage colony-stimulating factor Resorcinomycin 1995 [85] 1996 [86] Mycobacterium bovis Alveolar macrophages Rifampicin Liposomes 2009 [87] Mycobacterium tuberculosis…”