Penetration of topically used antimicrobials through Staphylococcus aureus biofilms: A comparative study using different models

Albayaty, Yassamin N.; Thomas, Nicky; Hasan, Sayeed; Prestidge, Clive A.

doi:10.1016/j.jddst.2018.10.015

Cited by 15 publications

(14 citation statements)

References 40 publications

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“…The MIC was determined by the broth dilution method following standard protocols [53,54]. Briefly, single colonies of S. aureus stable SCV blood isolate strain, WCH-SK2 [55] were diluted in 0.9% saline to 1 × 10 8 colony forming units (CFU)/mL (equivalent to an optical density of 0.08–0.12 at 600 nm).…”

Section: Methodsmentioning

confidence: 99%

Rifampicin-Loaded Mesoporous Silica Nanoparticles for the Treatment of Intracellular Infections

et al. 2019

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Infectious diseases remain a major burden in today’s world, causing high mortality rates and significant economic losses, with >9 million deaths per year predicted by 2030. Invasion of host cells by intracellular bacteria poses treatment challenges due to the poor permeation of antimicrobials into the infected cells. To overcome these limitations, mesoporous silica nanoparticles (MSNP) loaded with the antibiotic rifampicin were investigated as a nanocarrier system for the treatment of intracellular bacterial infection with specific interest in the influence of particle size on treatment efficiency. An intracellular infection model was established using small colony variants (SCV) of S. aureus in macrophages to systemically evaluate the efficacy of rifampicin-loaded MSNP against the pathogen as compared to a rifampicin solution. As hypothesized, the superior uptake of MSNP by macrophages resulted in an enhanced treatment efficacy of the encapsulated rifampicin as compared to free antibiotic. This study provides a potential platform to improve the performance of currently available antibiotics against intracellular infections.

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Section: Methodsmentioning

confidence: 99%

Rifampicin-Loaded Mesoporous Silica Nanoparticles for the Treatment of Intracellular Infections

et al. 2019

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“…This includes prevention of wash-out of an antimicrobial in the dynamic environment of the human body. In addition, antimicrobials may be enzymatically de-activated underway to a biofilm in the blood circulation or once inside a biofilm (Albayaty et al, 2018). Taken together, these factors make bacterial killing into the depth of a biofilm impossible (Sutherland, 2001), contributing to recurrence of infection after treatment (Wolfmeier et al, 2018).…”

Section: Traditional Problems In Antimicrobial Treatment Of Infectioumentioning

confidence: 99%

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

et al. 2020

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Many nanotechnology-based antimicrobials and antimicrobial-delivery-systems have been developed over the past decades with the aim to provide alternatives to antibiotic treatment of infectious-biofilms across the human body. Antimicrobials can be loaded into nanocarriers to protect them against de-activation, and to reduce their toxicity and potential, harmful side-effects. Moreover, antimicrobial nanocarriers such as micelles, can be equipped with stealth and pH-responsive features that allow self-targeting and accumulation in infectious-biofilms at high concentrations. Micellar and liposomal nanocarriers differ in hydrophilicity of their outer-surface and inner-core. Micelles are self-assembled, spherical core-shell structures composed of single layers of surfactants, with hydrophilic head-groups and hydrophobic tail-groups pointing to the micellar core. Liposomes are composed of lipids, self-assembled into bilayers. The hydrophilic head of the lipids determines the surface properties of liposomes, while the hydrophobic tail, internal to the bilayer, determines the fluidity of liposomal-membranes. Therefore, whereas micelles can only be loaded with hydrophobic antimicrobials, hydrophilic antimicrobials can be encapsulated in the hydrophilic, aqueous core of liposomes and hydrophobic or amphiphilic antimicrobials can be inserted in the phospholipid bilayer. Nanotechnology-derived liposomes can be prepared with diameters <100-200 nm, required to prevent reticulo-endothelial rejection and allow penetration into infectious-biofilms. However, surface-functionalization of liposomes is considerably more difficult than of micelles, which explains while self-targeting, pH-responsive liposomes that find their way through the blood circulation toward infectious-biofilms are still challenging to prepare. Equally, development of liposomes that penetrate over the entire thickness of biofilms to provide deep killing of biofilm inhabitants still provides a challenge. The liposomal phospholipid bilayer easily fuses with bacterial cell membranes to release high antimicrobial-doses directly inside bacteria. Arguably, protection against de-activation of antibiotics in liposomal nanocarriers and their fusogenicity constitute the biggest advantage of liposomal antimicrobial carriers over antimicrobials free in solution. Many Gram-negative and Gram-positive bacterial strains, resistant to specific antibiotics, Wang et al. Lipid-Based Antimicrobial Delivery-Systems have been demonstrated to be susceptible to these antibiotics when encapsulated in liposomal nanocarriers. Recently, also progress has been made concerning large-scale production and long-term storage of liposomes. Therewith, the remaining challenges to develop self-targeting liposomes that penetrate, accumulate and kill deeply in infectious-biofilms remain worthwhile to pursue.

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“…Due to a lack of target-specificity, a high concentration is often needed for 'naked' antimicrobial agents (without a drug delivery system) to exert the intended activities, which, however, can cause collateral tissue damage (Forier et al 2014). During the transportation in the circulatory system, the antimicrobial agents can potentially be de-activated by the immune system (Albayaty et al 2018). Therefore, a drug-vehicle is often needed for the antimicrobial agent to activate a 'stealth mode' to dodge the immuno-radar.…”

Section: Challenges In Traditional Antimicrobial Treatmentsmentioning

confidence: 99%

“…For this reason only, the dose of antimicrobials required to eliminate biofilms can be 1000-fold greater than that for planktonic cells (Mah and O'Toole 2001;Potera 2010). Moreover, the penetrated drug molecules may be inactivated enzymatically inside a biofilm (Albayaty et al 2018). Another aspect is that the cells submerged in the EPS matrix are often in a stationary (or dormant) phase of growth due to low levels of oxygen and nutrients (Smith 2005), which leads to a decreased susceptibility to the actions of chemotherapeutic agents that require active growth of microbes (Høiby et al 2011).…”

Section: Challenges In Traditional Antimicrobial Treatmentsmentioning

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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Penetration of topically used antimicrobials through Staphylococcus aureus biofilms: A comparative study using different models

Cited by 15 publications

References 40 publications

Rifampicin-Loaded Mesoporous Silica Nanoparticles for the Treatment of Intracellular Infections

Rifampicin-Loaded Mesoporous Silica Nanoparticles for the Treatment of Intracellular Infections

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

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

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