Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria

Liu, Yu Han; Kuo, Shuenn‐Wen; Yao, Bing; Fang, Zih Syun; Lee, Yi-Tzu; Chang, Yuan-Chih; Chen, Te Li; Hu, Che Ming Jack

doi:10.1016/j.actbio.2018.10.013

Cited by 43 publications

(33 citation statements)

References 46 publications

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“…The self-assembly of amphiphilic polypeptides was carried out by gradient phase inversion (dialysis) because of its simplicity and suitability for preparing self-assembled nanosystems [ 32 , 33 , 34 ]. The obtained suspensions were freeze-dried for storage.…”

Section: Resultsmentioning

confidence: 99%

“…For instance, Coppi et al developed a set of microparticles consisting of alginate and chitosan polyplexes for oral administration of polymyxin B [ 31 , 32 ]. Similarly, Liu et al prepared NPs by complexation of colistin with poly(glutamic acid) and further stabilized this delivery system with 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine- N -(methoxy (polyethylene glycol)-2000) [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E

et al. 2020

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Polymyxins are peptide antibiotics that are highly efficient against many multidrug resistant pathogens. However, the poor stability of polymyxins in the bloodstream requires the administration of high drug doses that, in turn, can lead to polymyxin toxicity. Consequently, different delivery systems have been considered for polymyxins to overcome these obstacles. In this work, we report the development of polymyxin delivery systems based on nanoparticles obtained from the self-assembly of amphiphilic random poly(l-glutamic acid-co-d-phenylalanine). These P(Glu-co-dPhe) nanoparticles were characterized in terms of their size, surface charge, stability, cytotoxicity, and uptake by macrophages. The encapsulation efficiency and drug loading into P(Glu-co-dPhe) nanoparticles were determined for both polymyxin B and E. The release kinetics of polymyxins B and E from nanoformulations was studied and compared in buffer solution and human blood plasma. The release mechanisms were analyzed using a number of mathematical models. The minimal inhibitory concentrations of the nanoformulations were established and compared with those determined for the free antibiotics.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E

et al. 2020

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“…Liu et al [108] developed nanoparticles of colistin (8 nm in size) by complexation of colistin with polyglutamic acid and subsequent stabilization with 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] ammonium salt (MW 2700). In vitro and in vivo studies showed that the colistin nanoparticles had equivalent antimicrobial activity against K. pneumoniae and A. baumannii to that of free colistin, but the particles showed improved safety and lower hepatotoxicity than the free drug when administered to mice over a seven-day period (the maximum tolerated dose increased 1.3-fold compared to free colistin).…”

Section: Polymeric Nano-and Microparticle Carriersmentioning

confidence: 99%

Polymyxin Delivery Systems: Recent Advances and Challenges

Dubashynskaya

Skorik

2020

Pharmaceuticals

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Polymyxins are vital antibiotics for the treatment of multiresistant Gram-negative ESKAPE pathogen infections. However, their clinical value is limited by their high nephrotoxicity and neurotoxicity, as well as their poor permeability and absorption in the gastrointestinal tract. This review focuses on various polymyxin delivery systems that improve polymyxin bioavailability and reduce drug toxicity through targeted and controlled release. Currently, the most suitable systems for improving oral, inhalation, and parenteral polymyxin delivery are polymer particles, liposomes, and conjugates, while gels, polymer fibers, and membranes are attractive materials for topical administration of polymyxin for the treatment of infected wounds and burns. In general, the application of these systems protects polymyxin molecules from the negative effects of both physiological and pathological factors while achieving higher concentrations at the target site and reducing dosage and toxicity. Improving the properties of polymyxin will be of great interest to researchers who are focused on developing antimicrobial drugs that show increased efficacy and safety.

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“…PMXs are positively charged, so they can interact with anionic phospholipids and anionic polymers; therefore, the modern delivery systems considered for PMXs include anionic liposomes [ 8 , 9 , 10 ] and anionic polymers. The anionic polymers form polyelectrolyte complexes (PECs) with PMXs due to electrostatic interactions [ 11 , 12 ]. For instance, Liu et al reported the preparation of nanoparticles (NPs) by complexation of colistin (polymyxin E) with poly(glutamic acid) and further stabilization of this delivery system using 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy (polyethylene glycol)-2000) [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Hybrid Nanoparticles and Composite Hydrogel Systems for Delivery of Peptide Antibiotics

Iudin

Vasilieva

Knyazeva

et al. 2022

IJMS

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The growing number of drug-resistant pathogenic bacteria poses a global threat to human health. For this reason, the search for ways to enhance the antibacterial activity of existing antibiotics is now an urgent medical task. The aim of this study was to develop novel delivery systems for polymyxins to improve their antimicrobial properties against various infections. For this, hybrid core–shell nanoparticles, consisting of silver core and a poly(glutamic acid) shell capable of polymyxin binding, were developed and carefully investigated. Characterization of the hybrid nanoparticles revealed a hydrodynamic diameter of approximately 100 nm and a negative electrokinetic potential. The nanoparticles demonstrated a lack of cytotoxicity, a low uptake by macrophages, and their own antimicrobial activity. Drug loading and loading efficacy were determined for both polymyxin B and E, and the maximal loaded value with an appropriate size of the delivery systems was 450 µg/mg of nanoparticles. Composite materials based on agarose hydrogel were prepared, containing both the loaded hybrid systems and free antibiotics. The features of polymyxin release from the hybrid nanoparticles and the composite materials were studied, and the mechanisms of release were analyzed using different theoretical models. The antibacterial activity against Pseudomonas aeruginosa was evaluated for both the polymyxin hybrid and the composite delivery systems. All tested samples inhibited bacterial growth. The minimal inhibitory concentrations of the polymyxin B hybrid delivery system demonstrated a synergistic effect when compared with either the antibiotic or the silver nanoparticles alone.

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Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria

Cited by 43 publications

References 46 publications

Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E

Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E

Polymyxin Delivery Systems: Recent Advances and Challenges

Hybrid Nanoparticles and Composite Hydrogel Systems for Delivery of Peptide Antibiotics

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