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Cefquinome-Loaded Microsphere Formulations in Protection against Pneumonia with Klebsiella pneumonia Infection and Inflammatory Response in Rats

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Abstract

Purpose

This study aimed to compare in vivo activity between cefquinome (CEQ)-loaded poly lactic-co-glycolic acid (PLGA) microspheres (CEQ-PLGA-MS) and CEQ injection (CEQ-INJ) against Klebsiella pneumonia in a rat lung infection model.

Methods

Forty-eight rats were divided into control group (sham operated without infection and drug treatment), Klebsiella pneumonia model group (KPD + Saline), CEQ-PLGA-MS and CEQ-INJ therapy groups (KPD + CEQ-PLGA-MS and KPD + INJ, respectively). In the KPD + Saline group, rats were infected with Klebsiella pneumonia ATCC 10031. In the KPD + CEQ-PLGA-MS and KPD + INJ groups, infected rats were intravenously injected with 12.5 mg/kg body weight CEQ-PLGA-MS and CEQ-INJ, respectively.

Results

Compared to CEQ-INJ treatment group, CEQ-PLGA-MS treatment further decreased the number of bacteria colonies (decreased to 1.94 lg CFU/g) in lung tissues and the levels of inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4 (p < 0.05 or p < 0.01) in bronchoalveolar lavage fluid at 48 h. Consistently, a significant decreases of scores of inflammation severity were showed at 48 h in the KPD + CEQ-PLGA-MS treatment group, compared to the KPD + CEQ-INJ treatment group.

Conclusion

Our results reveal that CEQ-PLGA-MS has the better therapeutic effect than CEQ-INJ for Klebsiella pneumonia lung infections in rats. The vehicle of CEQ-PLGA-MS as the promising alternatives to control the lung infections with the important pathogens.

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Abbreviations

BALF:

Bronchoalveolar lavage fluid

CEQ:

Cefquinome

CEQ-INJ:

CEQ injection

CEQ-PLGA-MS:

CEQ-loaded PLGA microspheres

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

IL:

Interleukin

i.v.:

Intravenously

K. pneumonia :

Klebsiella pneumonia

PD:

Pharmacodynamic

PLGA:

Poly lactic-co-glycolic acid

qRT-PCR :

Quantitative reverse transcription-PCR

RPMI:

Roswell Park Memorial Institute

SD:

Standard deviation

TNF:

Tumor necrosis factor

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by the national key research and development plan (NO. 2016YFD0501309) and startup and innovation leader talent plan of Qingdao 15–10–3-15-(41)-zch. The authors declare no conflicts of interest.

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Authors and Affiliations

  1. College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266109, China

    Shaoqi Qu, Cunchun Dai, Fenfang Yang, Tingting Huang, Zhihui Hao, Qihe Tang, Haixia Wang & Yanping Zhang

  2. National-Local Joint Engineering Laboratory of Agricultural Bio-pharmaceutical Technology, Qingdao, 266109, China

    Shaoqi Qu, Cunchun Dai, Fenfang Yang, Tingting Huang, Zhihui Hao, Qihe Tang, Haixia Wang & Yanping Zhang

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  1. Shaoqi Qu
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  2. Cunchun Dai
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Correspondence to Zhihui Hao.

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Qu, S., Dai, C., Yang, F. et al. Cefquinome-Loaded Microsphere Formulations in Protection against Pneumonia with Klebsiella pneumonia Infection and Inflammatory Response in Rats. Pharm Res 36, 74 (2019). https://doi.org/10.1007/s11095-019-2614-7

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