Polylactide-co-glycolide-rifampicin-nanoparticles efficiently clear<i>Mycobacterium bovis</i>BCG infection in macrophages and remain membrane-bound in phago-lysosomes

Kalluru, Raja; Fenaroli, Federico; Westmoreland, David; Ulanova, Lilia S.; Maleki, Atoosa; Roos, Norbert; Madsen, Marie Paulsen; Koster, Gerbrand; Egge-Jacobsen, Wolfgang; Wilson, Steven Ray; Røberg-Larsen, Hanne; Khuller, G. K.; Singh, Amandeep; Nyström, Bo; Griffiths, Gareth

doi:10.1242/jcs.121814

Cited by 97 publications

(90 citation statements)

References 53 publications

(72 reference statements)

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“…More groups supported this interpretation for different cell types, including macrophages [41][42][43]. On the other hand, the PLGA particles were suggested to remain within the phagolysosomal compartment for several days [44][45][46]. Another issue is the ability for PLGA particles to reach the compartment in which mycobacteria reside.…”

Section: Introductionmentioning

confidence: 97%

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Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Lemmer

Kalombo

Pietersen

et al. 2015

Journal of Controlled Release

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The appearance of drug-resistant strains of Mycobacterium tuberculosis (Mtb) poses a great challenge to the development of novel treatment programmes to combat tuberculosis. Since innovative nanotechnologies might alleviate the limitations of current therapies, we have designed a new nanoformulation for use as an anti-TB drug delivery system. It consists of incorporating mycobacterial cell wall mycolic acids (MA) as targeting ligands into a drug-encapsulating Poly dl-lactic-co-glycolic acid polymer (PLGA), via a double emulsion solvent evaporation technique. Bone marrow-derived mouse macrophages, either uninfected or infected with different mycobacterial strains (Mycobacterium avium, Mycobacterium bovis BCG or Mtb), were exposed to encapsulated isoniazid-PLGA nanoparticles (NPs) using MA as a targeting ligand. The fate of the NPs was monitored by electron microscopy. Our study showed that i) the inclusion of MA in the nanoformulations resulted in their expression on the outer surface and a significant increase in phagocytic uptake of the NPs; ii) nanoparticle-containing phagosomes were rapidly processed into phagolysosomes, whether MA had been included or not; and iii) nanoparticle-containing phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed.

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Section: Introductionmentioning

confidence: 97%

“…Another issue is the ability for PLGA particles to reach the compartment in which mycobacteria reside. One group suggested this possibility [47], but others could not demonstrate it [10,45].…”

Section: Introductionmentioning

confidence: 99%

Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Lemmer

Kalombo

Pietersen

et al. 2015

Journal of Controlled Release

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“…For example, using BCG-infected mice models, Griffith et al demonstrated the differential localization of BCG and PLGA nanoparticles within mouse primary macrophages. [37] When infecting macrophages, BCG predominantly resided within phagosomes. However, when drug-loaded PLGA nanoparticles were phagocytosed by macrophages, they instead localized to the phagolysosome (Figure 7).…”

Section: Polymer Nanoparticles As Anti-tb Drug Delivery Carriersmentioning

confidence: 99%

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections

Liang

Ding

et al. 2017

Adv Healthcare Materials

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worldwide was estimated at a staggering 10.4 million, with a significant percentage (10%) resulting from concomitant HIV-TB coinfections. [1] Given the closely knitted association between TB infections and poor sanitation/poverty, it thus comes with no surprise that an overwhelming majority of disease burden (60%) is actually shouldered by countries from the developing world (Figure 1). [1] TB infections are compounded by the emergence of multidrug resistance (MDR). In spite of the tremendous amount of resources and research dollars that have been devoted to TB research, TB diagnostics and treatment outcomes still remain startlingly poor. TB remains worryingly underreported, under-diagnosed and undertreated. A 4.3 million gap was reported between incident and notified TB cases, chiefly in developing countries; majority of TB infections remain latent and unreported, and only 30% of new incident TB cases were subjected to drug susceptibility testing. [1] The Xpert Mycobacterium Tuberculosis (MTB)/RIF assay remains the only available WHOrecommended rapid diagnostic platform for detection of TB and drug (rifampicin) resistance. Treatment success rates are highly variable, ranging from 28% (extensively drug-resistant strains) to 83% (garden strains) of TB. The rate of decline in TB incidence has remained stagnant at 1.5% annually over the past decade, far lagging behind the 5% projected by the WHO's End TB Strategy. Against such a backdrop, TB remains firmly entrenched among the top 10 causes of death worldwide. [2] To this end, the WHO has since 2015, adopted the End TB Strategy in an effort to stem this burgeoning epidemic. Major diagnostic and treatment gaps in TB management still remain, and these need to be addressed to effectively curtail TB spread and its impact on global health. Pathogenesis of TB InfectionsMTB is the infectious agent responsible for TB infections. It originates from the family Mycobacteriaceae and is an obligate bacteria chiefly spread via air droplets.

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“…PLGA-RIF NPs were prepared by single water-inoil-in-water emulsion solvent evaporation method and characterized by electron microscopy as described by Kalluru et al (2013).…”

Section: Plga Np and Nlc Preparationmentioning

confidence: 99%

Treatment of Francisella infections via PLGA- and lipid-based nanoparticle delivery of antibiotics in a zebrafish model

Ulanova

Pinheiro²,

Vibe³

et al. 2017

Dis. Aquat. Org.

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We tested the efficiency of 2 different antibiotics, rifampicin and oxolinic acid, against an established infection caused by fish pathogen Francisella noatunensis ssp. orientalis (F.n.o.) in zebrafish. The drugs were tested in the free form as well as encapsulated into biodegradable nanoparticles, either polylactic-co-glycolic acid (PLGA) nanoparticles or nanostructured lipid carriers. The most promising therapies were PLGA-rifampicin nanoparticles and free oxolinic acid; the PLGA nanoparticles significantly delayed embryo mortality while free oxolinic acid prevented it. Encapsulation of rifampicin in both PLGA and nanostructured lipid carriers enhanced its efficiency against F.n.o. infection relative to the free drug. We propose that the zebrafish model is a robust, rapid system for initial testing of different treatments of bacterial diseases important for aquaculture.

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Polylactide-co-glycolide-rifampicin-nanoparticles efficiently clearMycobacterium bovisBCG infection in macrophages and remain membrane-bound in phago-lysosomes

Cited by 97 publications

References 53 publications

Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections

Treatment of Francisella infections via PLGA- and lipid-based nanoparticle delivery of antibiotics in a zebrafish model

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