Chitosan nanoparticles loaded with the antimicrobial peptide temporin B exert a long-term antibacterial activity in vitro against clinical isolates of Staphylococcus epidermidis

Abstract

Nowadays, the alarming rise in multidrug-resistant microorganisms urgently demands for suitable alternatives to current antibiotics. In this regard, antimicrobial peptides (AMPs) have received growing interest due to their broad spectrum of activities, potent antimicrobial properties, unique mechanisms of action, and low tendency to induce resistance. However, their pharmaceutical development is hampered by potential toxicity, relatively low stability and manufacturing costs. In the present study, we tested the hypothesis that the encapsulation of the frog-skin derived AMP temporin B (TB) into chitosan nanoparticles (CS-NPs) could increase peptide’s antibacterial activity, while reducing its toxic potential. TB-loaded CS-NPs with good dimensional features were prepared, based on the ionotropic gelation between CS and sodium tripolyphosphate. The encapsulation efficiency of TB in the formulation was up to 75%. Release kinetic studies highlighted a linear release of the peptide from the nanocarrier, in the adopted experimental conditions. Interestingly, the encapsulation of TB in CS-NPs demonstrated to reduce significantly the peptide’s cytotoxicity against mammalian cells. Additionally, the nanocarrier evidenced a sustained antibacterial action against various strains of Staphylococcus epidermidis for at least 4 days, with up to 4-log reduction in the number of viable bacteria compared to plain CS-NPs at the end of the observational period. Of note, the antimicrobial evaluation tests demonstrated that while the intrinsic antimicrobial activity of CS ensured a “burst” effect, the gradual release of TB further reduced the viable bacterial count, preventing the regrowth of the residual cells and ensuring a long-lasting antibacterial effect. The developed nanocarrier is eligible for the administration of several AMPs of therapeutic interest with physical–chemical characteristics analog to those of TB.

Anti-biofilm properties of the antimicrobial peptide temporin 1Tb and its ability, in combination with EDTA, to eradicate Staphylococcus epidermidis biofilms on silicone catheters

“…The peptide was previously shown to display rapid killing effects against multi-drug-resistant, clinically relevant, bacterial pathogens and particularly against Gram-positive species (Mangoni et al 2008). Recently it has been reported that TB, encapsulated in chitosan nanoparticles, is able to exert a strong and prolonged bactericidal effect against numerous clinical isolates of S. epidermidis (Piras et al 2015). Interestingly, it has been also demonstrated that the peptide is able to penetrate eukaryotic cells, kill intracellular bacteria, and promote wound-healing (Di Grazia et al 2014).…”

An investigation of the interactions between an E. coli bacterial quorum sensing biosensor and chitosan-based nanocapsules

“…Disruption of bacterial QS either using specific inhibitors that compete with or enzymes that degrade AHLs, without exerting toxicity, is considered as a promising approach to circumvent bacterial drug-resistance and a route to the development of a new generation of medicines to deal with bacterial infections Particles produced from inorganic substances such as metals, or silica, ranging in size from a few nanometers to the micrometer length scale, have extensively been studied for their use in antibacterial control [24][25][26]. Also, particles comprising organic building blocks such as polymers, lipids, or proteins of a different type, have been used to prepare antibiotic-loaded formulations for controlled drug delivery [27][28][29]. In particular, in the recent years, an increasing number of studies have focused on exploring the impacts of nanomaterials on bacterial QS signaling.…”

Nano-encapsulated HHC10 host defense peptide (HDP) reduces the growth of Escherichia coli via multimodal mechanisms

“…Host defense peptides (HDP) are promising antibacterial compounds considered to be promising candidates due to their broad range of activity and multiple mechanism of action [9][10][11] which leads to less resistance developed by the bacteria so HDP are new popular topic for research all over the world [12][13][14]. The broad spectrum of HDP makes them suitable for future medical applications; in this sense, nanotechnology provides promising support for peptide transport and targeted delivery with strongly enhanced biocidal properties and significant reduction of toxicity [15][16][17][18]. Indeed, there are many HDP under clinical developments for treating wide variety of diseases [19].…”