The behavior of PLGA microspheres containing rifampicin in alveolar macrophages

Onoshita, T.; Shimizu, Yasuhiko; Yamaya, Naomitsu; Miyazaki, Masao; Yokoyama, Masayuki; Fujiwara, N.; Nakajima, Taro; Makino, Kimiko; Terada, Hiroshi; Haga, Makoto

doi:10.1016/j.colsurfb.2009.10.036

Cited by 48 publications

(24 citation statements)

References 36 publications

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“…However, as pointed out by Makino et al rifampicin is less soluble at pH 4 than at pH 7 (Makino, 2004). Our results are essentially identical to figure 2 in the study of Onoshita and co-workers using PLGA-rifampicin NPs (Onoshita, 2010).…”

Section: Fabrication and Characterization Of Plga Nanoparticlessupporting

confidence: 90%

“…It was reported that there was no visible colocalization of NPs and bacteria. In the paper by (Onoshita et al, 2010), between 80 and 90% of the PLGA MPs enclosing the green fluorescent dye coumarin-6, colocalized with vesicles labeled with the low pH vital dye LysoTracker Red for at least 7 days in a rat alveolar macrophage cell line. It is agreed in the field that only a small fraction of M.tb (and BCG) are found in LysoTracker-positive late endosomes and lysosomes (simplified in the rest of this paper collectively as 'lysosomes') in macrophages (Jordao et al, 2008).…”

Section: Introductionmentioning

confidence: 97%

“…A few of these cell-level studies have also encapsulated a fluorescent dye (without antibiotics) inside PLGA or other polymer particles, in order to follow their localization in cells (Jain et al, 2010;Kisich et al, 2007;Onoshita et al, 2010). The Kisich et al study (Kisich et al, 2007) infected macrophages with Oregon Green surface-labeled M.tb and additionally internalized rhodamine-labeled polybutyl-cyanoacrylate PBCA particles.…”

Section: Introductionmentioning

confidence: 99%

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

Kalluru

Fenaroli

Westmoreland

et al. 2013

Journal of Cell Science

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Summary Nanoparticles (NPs) are increasingly used as biodegradable vehicles to selectively deliver therapeutic agents such as drugs or antigens to cells. The most widely used vehicle for this purpose is based on copolymers of lactic acid and glycolic acid (PLGA) and has been extensively used in experiments aimed at delivering antibiotics against Mycobacterium tuberculosis in animal models of tuberculosis. Here, we describe fabrication of PLGA NPs containing either a high concentration of rifampicin or detectable levels of the green fluorescent dye, coumarin-6. Our goal here was twofold: first to resolve the controversial issue of whether, after phagocytic uptake, PLGA NPs remain membrane-bound or whether they escape into the cytoplasm, as has been widely claimed. Second, we sought to make NPs that enclosed sufficient rifampicin to efficiently clear macrophages of infection with Mycobacterium bovis BCG. Using fluorescence microscopy and immuno-electron microscopy, in combination with markers for lysosomes, we show that BCG bacteria, as expected, localized to early phagosomes, but that at least 90% of PLGA particles were targeted to, and remained in, low pH, hydrolaserich phago-lysosomes. Our data collectively argue that PLGA NPs remain membrane-enclosed in macrophages for at least 13 days and degrade slowly. Importantly, provided that the NPs are fabricated with sufficient antibiotic, one dose given after infection is sufficient to efficiently clear the BCG infection after 9-12 days of treatment, as shown by estimates of the number of bacterial colonies in vitro.

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Section: Fabrication and Characterization Of Plga Nanoparticlessupporting

confidence: 90%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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

Kalluru

Fenaroli

Westmoreland

et al. 2013

Journal of Cell Science

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“…Tuberculosis (TB) is one of the most deadly diseases affecting mankind (1,2). It is caused by bacillus Mycobacterium tuberculosis (MTB), a facultative intracellular parasite (3,4).…”

Section: Introductionmentioning

confidence: 99%

In Vitro-In Vivo Evaluation of Novel Co-spray Dried Rifampicin Phospholipid Lipospheres for Oral Delivery

Singh¹,

Koduri²,

Bhatt³

et al. 2016

AAPS PharmSciTech

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Abstract. The objective of this study comprises of developing novel co-spray dried rifampicin phospholipid lipospheres (SDRPL) to investigate its influence on rifampicin solubility and oral bioavailability. Solid-state techniques were employed to characterize the liposphere formulation. SDRPL solubility was determined in distilled water. BACTEC 460TB System was employed to evaluate SDRPL antimycobacterial activity. The oral bioavailability of the lipospheres was evaluated in Sprague Dawley rats. Lipospheres exhibited amorphous, smooth spherical morphology with a significant increase (p < 0.001) in solubility of SDRPL (2:1), 350.9 ± 23 versus 105.1 ± 12 μg/ml and SDRPL (1:1) 306.4 ± 20 versus 105.1 ± 12 μg/ml in comparison to rifampicin (RMP). SDRPL exhibited enhanced activity against Mycobacterium tuberculosis, H37Rv strain, with over twofolds less minimum inhibitory concentration (MIC) than the free drug. Lipospheres exhibited higher peak plasma concentration (109.92 ± 25 versus 54.31 ± 18 μg/ml), faster T max (two versus four hours), and enhanced area under the curve (AUC 0-∞ ) (406.92 ± 18 versus 147.72 ± 15 μg h/L) in comparison to pure RMP. Thus, SDRPL represents a promising carrier system exhibiting enhanced antimycobacterial activity and oral bioavailability of rifampicin.

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“…39 These factors may lead to low patient compliance and contribute to the development of drug-resistant bacteria. 40 …”

Section: Tuberculosismentioning

confidence: 99%

Nanomedicine as an emerging approach against intracellular pathogens

Armstead¹,

Li²

2011

IJN

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Diseases such as tuberculosis, hepatitis, and HIV/AIDS are caused by intracellular pathogens and are a major burden to the global medical community. Conventional treatments for these diseases typically consist of long-term therapy with a combination of drugs, which may lead to side effects and contribute to low patient compliance. The pathogens reside within intracellular compartments of the cell, which provide additional barriers to effective treatment. Therefore, there is a need for improved and more effective therapies for such intracellular diseases. This review will summarize, for the first time, the intracellular compartments in which pathogens can reside and discuss how nanomedicine has the potential to improve intracellular disease therapy by offering properties such as targeting, sustained drug release, and drug delivery to the pathogen’s intracellular location. The characteristics of nanomedicine may prove advantageous in developing improved or alternative therapies for intracellular diseases.

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The behavior of PLGA microspheres containing rifampicin in alveolar macrophages

Cited by 48 publications

References 36 publications

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

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

In Vitro-In Vivo Evaluation of Novel Co-spray Dried Rifampicin Phospholipid Lipospheres for Oral Delivery

Nanomedicine as an emerging approach against intracellular pathogens

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