A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms

Baek, Jong-Suep; Tan, Chuan Hao; Ng, Noele Kai Jing; Yeo, Yee Phan; Rice, Scott A.; Loo, Say Chye Joachim

doi:10.1039/c7nh00167c

Cited by 34 publications

(31 citation statements)

References 37 publications

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“…The positive surface charge also provides higher binding affinity toward both planktonic bacteria and biofilms, providing localized delivery and minimizing systemic exposure, whereas the polymeric core contributes to the sustained antibiotic release to bacterial biofilms shown in our previous study. 21 On the basis of our conjecture from previous studies, LPNs can be engulfed by the professional phagocytes through phagocytosis, which is the same transport pathway as pathogens. This allows the loaded antibiotic to be delivered into the infected cells, thereby enhancing its penetration against intracellular pathogens.…”

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confidence: 88%

Lipid-Polymer Hybrid Nanoparticles Enhance the Potency of Ampicillin against Enterococcus faecalis in a Protozoa Infection Model

Tan

Jiang

et al. 2021

ACS Infect. Dis.

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Enterococcus faecalis ( E. faecalis ) biofilms are implicated in endocarditis, urinary tract infections, and biliary tract infections. Coupled with E. faecalis internalization into host cells, this opportunistic pathogen poses great challenges to conventional antibiotic therapy. The inability of ampicillin (Amp) to eradicate bacteria hidden in biofilms and intracellular niches greatly reduces its efficacy against complicated E. faecalis infections. To enhance the potency of Amp against different forms of E. faecalis infections, Amp was loaded into Lipid-Polymer hybrid Nanoparticles (LPNs), a highly efficient nano delivery platform consisting of a unique combination of DOTAP lipid shell and PLGA polymeric core. The antibacterial activity of these nanoparticles (Amp-LPNs) was investigated in a protozoa infection model, achieving a much higher multiplicity of infection (MOI) compared with studies using animal phagocytes. A significant reduction of total E. faecalis was observed in all groups receiving 250 μg/mL Amp-LPNs compared with groups receiving the same concentration of free Amp during three different interventions, simulating acute and chronic infections and prophylaxis. In early intervention, no viable E. faecalis was observed after 3 h LPNs treatment whereas free Amp did not clear E. faecalis after 24 h treatment. Amp-LPNs also greatly enhanced the antibacterial activity of Amp at late intervention and boosted the survival rate of protozoa approaching 400%, where no viable protozoa were identified in the free Amp groups at the 40 h postinfection treatment time point. Prophylactic effectiveness with Amp-LPNs at a concentration of 250 μg/mL was exhibited in both bacteria elimination and protozoa survival toward subsequent infections. Using protozoa as a surrogate model for animal phagocytes to study high MOI infections, this study suggests that LPN-formulated antibiotics hold the potential to significantly improve the therapeutic outcome in highly complicated bacterial infections.

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confidence: 88%

Lipid-Polymer Hybrid Nanoparticles Enhance the Potency of Ampicillin against Enterococcus faecalis in a Protozoa Infection Model

Tan

Jiang

et al. 2021

ACS Infect. Dis.

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“…Liposome composed of soy lecithin and cholesterol (5 : 1) was found to extend the stable period of cinnamon oil for 96 h and enhance its anti-biofilm activities against MRSA by over ten times, as compared to free cinnamon oil (Cui et al 2016). In context of the horizontal transmission of antimicrobial resistance genes, liposomes can not only efficiently 'sneak' into the interior of a biofilm, but also 'mask' the encapsulated drug from the cells until it reaches its destination and burst, so that the cells do not immediately recognize the 'intruder' and develop resistance through gene transfer (Van Bambeke et al 2008;Meng et al 2016;Rukavina and Vanic 2016;Baek et al 2018;Ramos et al 2018). For instance, it was reported that wheat germ agglutinin-modified liposomes as a drug carrier enhanced the antimicrobial efficiency of clarithromycin against MRSA by overcoming several resistance-associated phenotypic changes such as thickened cell wall and overexpression of efflux pumps (Meng et al 2016).…”

Section: Advantages and Limitations Of Liposome As A Drug Carriermentioning

confidence: 99%

Liposome as a delivery system for the treatment of biofilm‐mediated infections

Wang

2021

J Appl Microbiol

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Biofilm formation by pathogenic microorganisms has been a tremendous challenge for antimicrobial therapies due to various factors. The biofilm matrix sequesters bacterial cells from the exterior environment and therefore prevents antimicrobial agents from reaching the interior. In addition, biofilm surface extracellular polymeric substances can absorb antimicrobial agents and thus reduce their bioavailability. To conquer these protection mechanisms, liposomes have been developed into a drug delivery system for antimicrobial agents against biofilm-mediated infections. The unique characteristics of liposomes, including versatility for cargoes, target-specificity, nonimmunogenicity, low toxicity, and biofilm matrix-/cell membranefusogenicity, remarkably improve the effectiveness of antimicrobial agents and minimize recurrence of infections. This review summarizes current development of liposomal carriers for biofilm therapeutics, presents evidence in their practical applications and discusses their potential limitations.

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“…However, it was observed that the phosphatidylcholine (PC)-based monolayer on the hybrid nanoparticles did not prompt the biofilm affinity. In contrast, a cationic lipid (i.e., 1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) shell enabled the LPNPs to anchor onto surfaces of a diverse range of Gram-positive and Gram-negative bacterial pathogens [148]. However, the positive charge may impair the mucus-penetrating property, thus be inefficient in the treatment of respiratory tract infections.…”

Section: Lipid-enveloped Polymeric Nanoparticlesmentioning

confidence: 99%

Nanoparticle-mediated pulmonary drug delivery: state of the art towards efficient treatment of recalcitrant respiratory tract bacterial infections

Huang

Kłodzińska

Wan

et al. 2021

Drug Deliv. and Transl. Res.

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Graphical abstract Recalcitrant respiratory tract infections caused by bacteria have emerged as one of the greatest health challenges worldwide. Aerosolized antimicrobial therapy is becoming increasingly attractive to combat such infections, as it allows targeted delivery of high drug concentrations to the infected organ while limiting systemic exposure. However, successful aerosolized antimicrobial therapy is still challenged by the diverse biological barriers in infected lungs. Nanoparticle-mediated pulmonary drug delivery is gaining increasing attention as a means to overcome the biological barriers and accomplish site-specific drug delivery by controlling release of the loaded drug(s) at the target site. With the aim to summarize emerging efforts in combating respiratory tract infections by using nanoparticle-mediated pulmonary delivery strategies, this review provides a brief introduction to the bacterial infection-related pulmonary diseases and the biological barriers for effective treatment of recalcitrant respiratory tract infections. This is followed by a summary of recent advances in design of inhalable nanoparticle-based drug delivery systems that overcome the biological barriers and increase drug bioavailability. Finally, challenges for the translation from exploratory laboratory research to clinical application are also discussed and potential solutions proposed.

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A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms

Abstract: Lipid-polymer hybrid nanoparticle enhances antibiotic efficacy through localised, sustained delivery to bacterial biofilms.

Cited by 34 publications

References 37 publications

Lipid-Polymer Hybrid Nanoparticles Enhance the Potency of Ampicillin against Enterococcus faecalis in a Protozoa Infection Model

Lipid-Polymer Hybrid Nanoparticles Enhance the Potency of Ampicillin against Enterococcus faecalis in a Protozoa Infection Model

Liposome as a delivery system for the treatment of biofilm‐mediated infections

Nanoparticle-mediated pulmonary drug delivery: state of the art towards efficient treatment of recalcitrant respiratory tract bacterial infections

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