An inflammation-targeted nanoparticle with bacteria forced release of polymyxin B for pneumonia therapy

Zhang, Peisen; Ouyang, Qiuhong; Zhai, Tianshu; Sun, Jing; Wu, Jun; Qin, Feng; Zhang, Ni; Yue, Saisai; Yang, Xiaopei; Zhang, Hanyi; Hou, Yi; Deng, Li; Wang, Fang; Zhan, Qingyuan; Yu, Qingsong; Qin, Meng; Gan, Zhihua

doi:10.1039/d2nr02026b

Cited by 18 publications

(12 citation statements)

References 42 publications

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“…This result showed that D‐J‐1 could exert potent in vivo antimicrobial activity in the body of an animal model. Due to bacterial infections that could trigger the inflammation response and impede the wound healing process on the body surface or in vivo, [ 21 ] the antimicrobial activity would be an advantage of D‐J‐1 hydrogel and expand its applications.…”

Section: Resultsmentioning

confidence: 99%

The Antimicrobial, Hemostatic, and Anti‐Adhesion Effects of a Peptide Hydrogel Constructed by the All‐d‐Enantiomer of Antimicrobial Peptide Jelleine‐1

Zhang

Zhou

et al. 2023

Adv Healthcare Materials

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Peptide hydrogels were believed to be potential biomaterials with wide application in the biomedical field because of their good biocompatibility, injectability, and three‐dimensional (3D) printability. Most of the previously reported polypeptide hydrogels are composed of L‐peptides, while the hydrogels formed by self‐assembly of D‐peptides are rarely reported. Herein, we reported a peptide hydrogel constructed by D‐J‐1, which was the all‐D‐enantiomer of antimicrobial peptide Jelleine‐1. Field emission scanning electron microscope (FE‐SEM) and rheologic study were performed to characterize the hydrogel. Antimicrobial, hemostatic, and anti‐adhesion studies were carried out to evaluate its biofunction. Our results showed that D‐J‐1 hydrogel was formed by self‐assembly and cross‐linking driven by hydrogen bonding, hydrophobic interaction, and π‐π stacking force of aromatic ring in the structure of D‐J‐1. It exhibited promising antimicrobial activity, hemostatic activity, and anti‐adhesion efficiency in a rat sidewall defect‐cecum abrasion model. In addition, it also exhibited good biocompatibility. Notably, D‐J‐1 hydrogel showed improved in vitro and in vivo stability when compared with its L‐enantiomer J‐1 hydrogel. Therefore, the present study would provide new insight into the application of D‐peptide hydrogel, and provide a new peptide hydrogel with antibacterial, hemostatic, and anti‐adhesion efficacy for clinical use.This article is protected by copyright. All rights reserved

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Section: Resultsmentioning

confidence: 99%

The Antimicrobial, Hemostatic, and Anti‐Adhesion Effects of a Peptide Hydrogel Constructed by the All‐d‐Enantiomer of Antimicrobial Peptide Jelleine‐1

Zhang

Zhou

et al. 2023

Adv Healthcare Materials

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“…Furthermore, by reducing the positive charge of PMB, PMB-HA nanoparticles reduce cellular damage as well as histological toxicity, thus improving cellular and biological safety. This intelligent delivery system provides a new approach for the resurrection of PMB in the treatment of bacterial inflammatory diseases [ 115 ].…”

Section: Bioactive Nanoparticles For the Treatment Of Bacterial Infec...mentioning

confidence: 99%

“… Schematic illustration of the construction of inflammation-targeted smart nanoparticles PMB-HA, together with the molecular mechanism of their bacteria-triggered PMB-forced-release ability to precisely kill the pneumonia bacteria with outstanding biosafety. Modified and reproduced with permission from the Royal Society of Chemistry [ 115 ]. …”

Section: Figurementioning

confidence: 99%

Nanomaterials for Delivering Antibiotics in the Therapy of Pneumonia

Tang

Ouyang

et al. 2022

IJMS

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Bacterial pneumonia is one of the leading causes of death worldwide and exerts a significant burden on health-care resources. Antibiotics have long been used as first-line drugs for the treatment of bacterial pneumonia. However, antibiotic therapy and traditional antibiotic delivery are associated with important challenges, including drug resistance, low bioavailability, and adverse side effects; the existence of physiological barriers further hampers treatment. Fortunately, these limitations may be overcome by the application of nanotechnology, which can facilitate drug delivery while improving drug stability and bioavailability. This review summarizes the challenges facing the treatment of bacterial pneumonia and also highlights the types of nanoparticles that can be used for antibiotic delivery. This review places a special focus on the state-of-the-art in nanomaterial-based approaches to the delivery of antibiotics for the treatment of pneumonia.

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“…The aim of this study was therefore to develop a delivery system protecting polypeptide antibiotics against enzymatic degradation and enabling their transport across the mucus gel layer by the design of polyphosphate NPs. As a model polypeptide antibiotic polymyxin B (PMB) being used for the treatment of multidrug-resistant (MDR) infections in the eye, ear, skin, and bloodstream was chosen because of its cationic charge and since it can be administrated just via intravenous, intramuscular, pulmonary, intrathecal, and topical routes. , Furthermore, various studies have already shown that PMB can be efficiently complexed with anionic polymers forming NPs through electrostatic interactions. , The formation of stable complexes between PMB and polyphosphate (PP) should thus be feasible and might enable us to form NPs even without any cationic polymeric excipients that pose a safety concern. Furthermore, a protective effect of the peptide toward enzymatic degradation should be provided.…”

Section: Introductionmentioning

confidence: 99%

Peptide Antibiotic–Polyphosphate Nanoparticles: A Promising Strategy to Overcome the Enzymatic and Mucus Barrier of the Intestine

et al. 2023

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The aim of this study was to develop peptide antibiotic–polyphosphate nanoparticles that are able to overcome the enzymatic and mucus barriers providing a targeted drug release directly on the intestinal epithelium. Polymyxin B–polyphosphate nanoparticles (PMB–PP NPs) were formed via ionic gelation between the cationic peptide and the anionic polyphosphate (PP). The resulting NPs were characterized by particle size, polydispersity index (PDI), zeta potential, and cytotoxicity on Caco-2 cells. The protective effect of these NPs for incorporated PMB was evaluated via enzymatic degradation studies with lipase. Moreover, mucus diffusion of NPs was investigated with porcine intestinal mucus. Isolated intestinal alkaline phosphatase (IAP) was employed to trigger the degradation of NPs and consequent drug release. PMB–PP NPs exhibited an average size of 197.13 ± 14.13 nm, a PDI of 0.36, a zeta potential of −11.1 ± 3.4 mV and a concentration and time-dependent toxicity. They provided entire protection toward enzymatic degradation and exhibited significantly (p < 0.05) higher mucus permeating properties than PMB. When incubated with isolated IAP for 4 h, monophosphate and PMB were constantly released from PMB–PP NPs and zeta potential raised up to −1.9 ± 0.61 mV. According to these findings, PMB–PP NPs are promising delivery systems to protect cationic peptide antibiotics against enzymatic degradation, to overcome the mucus barrier and to provide drug release directly at the epithelium.

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An inflammation-targeted nanoparticle with bacteria forced release of polymyxin B for pneumonia therapy

Abstract: The epidemic of multidrug-resistant gram-negative bacteria is an ever-growing global concern. Polymyxin B (PMB), a kind of “old fashioned” antibiotic, has been revived in clinical practice and mainly used as...

Cited by 18 publications

References 42 publications

The Antimicrobial, Hemostatic, and Anti‐Adhesion Effects of a Peptide Hydrogel Constructed by the All‐d‐Enantiomer of Antimicrobial Peptide Jelleine‐1

The Antimicrobial, Hemostatic, and Anti‐Adhesion Effects of a Peptide Hydrogel Constructed by the All‐d‐Enantiomer of Antimicrobial Peptide Jelleine‐1

Nanomaterials for Delivering Antibiotics in the Therapy of Pneumonia

Peptide Antibiotic–Polyphosphate Nanoparticles: A Promising Strategy to Overcome the Enzymatic and Mucus Barrier of the Intestine

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