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Targeted Delivery of Antibiotics to the Infected Pulmonary Tissues Using ROS-responsive Nanoparticles

Targeted Delivery of Antibiotics to the Infected Pulmonary Tissues Using ROS-responsive Nanoparticles

Yu Wang, Qian Yuan, Wei Feng, Wendan Pu, Jun Ding, Hongjun Zhang, Xiaoyu Li, Bo Yang, Qing Dai, Lin Cheng, Jinyu Wang, Fengjun Sun, Dinglin Zhang

J Nanobiotechnology. 2019 Oct 3;17(1):103.

PMID: 31581948

Abstract:

Background:
Immunocompromised individuals and those with lung dysfunction readily acquire pulmonary bacterial infections, which may cause serious diseases and carry a heavy economic burden. Maintaining adequate antibiotic concentrations in the infected tissues is necessary to eradicate resident bacteria. To specifically deliver therapeutics to the infected pulmonary tissues and enable controlled release of payloads at the infection site, a ROS-responsive material, i.e. 4-(hydroxymethyl) phenylboronic acid pinacol ester-modified α-cyclodextrin (Oxi-αCD), was employed to encapsulate moxifloxacin (MXF), generating ROS-responsive MXF-containing nanoparticles (MXF/Oxi-αCD NPs).
Results:
MXF/Oxi-αCD NPs were coated with DSPE-PEG and DSPE-PEG-folic acid, facilitating penetration of the sputum secreted by the infected lung and enabling the active targeting of macrophages in the inflammatory tissues. In vitro drug release experiments indicated that MXF release from Oxi-αCD NPs was accelerated in the presence of 0.5 mM H2O2. In vitro assay with Pseudomonas aeruginosa demonstrated that MXF/Oxi-αCD NPs exhibited higher antibacterial activity than MXF. In vitro cellular study also indicated that folic acid-modified MXF/Oxi-αCD NPs could be effectively internalized by bacteria-infected macrophages, thereby significantly eradicating resident bacteria in macrophages compared to non-targeted MXF/Oxi-αCD NPs. In a mouse model of pulmonary P. aeruginosa infection, folic acid-modified MXF/Oxi-αCD NPs showed better antibacterial efficacy than MXF and non-targeted MXF/Oxi-αCD NPs. Meanwhile, the survival time of mice was prolonged by treatment with targeting MXF/Oxi-αCD NPs.
Conclusions:
Our work provides a strategy to overcome the mucus barrier, control drug release, and improve the targeting capability of NPs for the treatment of pulmonary bacterial infections.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP1217891718	9-Methyl-9H-carbazole-3-boronic acid pinacol ester	1217891-71-8	Price
AP126726623	Isopropenylboronic acid pinacol ester	126726-62-3	Price
AP269410222	4-Hydroxy-3-methoxyphenylboronic acid pinacol ester	269410-22-2	Price
AP388116276	Indole-4-boronic acid pinacol ester	388116-27-6	Price
AP936250178	2,4-Dimethoxypyrimidine-5-boronic acid pinacol ester	936250-17-8	Price
AP936902124	Benzooxazole-5-boronic acid pinacol ester	936902-12-4	Price
LS793293	cis-Stilbeneboronic acid pinacol ester		Price
LS793309	2-picoline-5-boronic acid pinacol ester		Price

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