Interactions of the antimicrobial peptide nisin Z with conventional antibiotics and the use of nanostructured lipid carriers to enhance antimicrobial activity (original) (raw)
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Antimicrobial Peptides and Nanotechnology, Recent Advances and Challenges
Frontiers in microbiology, 2018
Antimicrobial peptides are sequences of amino acids, which present activity against microorganisms. These peptides were discovered over 70 years ago, and are abundant in nature from soil bacteria, insects, amphibians to mammals and plants. They vary in amino acids number, the distance between amino acids within individual peptide structure, net charge, solubility and other physical chemical properties as well as differ in mechanism of action. These peptides may provide an alternative treatment to conventional antibiotics, which encounter resistance such as the peptide nisin applied in treating methicillin resistant (MRSA) or may behave synergistically with known antibiotics against parasites for instance, nisin Z when used in synergy with ampicillin reported better activity against than when the antibiotic was alone. AMPs are known to be active against viruses, bacteria, fungi and protozoans. Nanotechnology is an arena which explores the synthesis, characterization and application o...
Production of nisin-loaded solid lipid nanoparticles for sustained antimicrobial activity
Food Control, 2012
Nisin is a natural antimicrobial agent that is used as a preservative in heat processed and low pH foods. However, its bioactivity is lost by interaction with food components. Slow release nisin-loaded solid lipid nanoparticles (SLN) were produced by high pressure homogenization to provide protection from the food environment and prolong the biological activity. The optimized conditions for the preparation of Imwitor 900 based SLNs was a pressure of 1500 bars in a high pressure homogenizer for three cycles, with 5% (w/v) poloxamer 188 and 0.125% (w/v) sodium deoxycholate as the surfactant and co-surfactant, respectively. Unloaded SLN produced under this condition had the smallest nanometric particle size (119 AE 15.1 nm) with a narrow polydispersity (0.38 AE 0.03). Nisin-loaded SLNs, prepared from 0.5 to 3.0% (w/w) nisin, were larger than the unloaded SLN, with a size range of 159 AE 6.4e167 AE 8.6 nm, had a zetapotential of À28.3 AE 0.15 to À29.2 AE 0.12 mV and nisin entrapment efficiency of 69.2 AE 0.04 e73.6 AE 0.04%, the optimal being at 2% (w/w) nisin. During 28 day of aqueous suspension at 30 C, the size of the SLNs increased to 214 AE 10.8e245 AE 15.7 nm and zeta-potential decreased to À21.6 AE 0.43 to À25.9 AE 0.34 mV. Scanning electron microscopy (SEM) demonstrated that nanoparticles had platelet shape. In vitro release studies revealed that nisin was released from the SLNs throughout the 25 day period but the release rate decreased as the pH of buffer increased from 2.0 to 7.4 and as the salt concentration increased, up to 0.5 M sodium chloride, whereupon high nisin was released within the first day. The antibacterial activity of nisin-loaded SLNs against Listeria monocytogenes DMST 2871 and Lactobacillus plantarum TISTR 850 was evident for up to 20 and 15 days, respectively, compared to only one and three days, respectively, for free nisin.
Nanomedicine, 2019
Aim: Over the last decade, antimicrobial peptides (AMPs) have emerged as a promising alternative for the treatment of various infections. The aim of this work is to explore the potential of lipid nanocapsules for the delivery of AMPs. Three approaches were compared in terms of encapsulation efficiency, peptide activity and protection against proteases: peptide encapsulation, surface adsorption or covalent attachment of three selected AMPs. Results: A potentiation of the antimicrobial activity and a partial protection of the peptides after adsorption were demonstrated compared with native peptides. Conversely, encapsulation allowed better peptide stability, correlated with higher encapsulation efficiencies and a preservation of the activity. Finally, the covalent attachment strategy turned out to be less conclusive due to peptide inactivation. Conclusion: In brief, a lipid nanocapsule-based platform appears suitable to deliver AMPs.
Pharmaceutics, 2022
At present, antibiotic resistance is considered a real problem. Therefore, for decades scientists have been looking for novel strategies to treat bacterial infections. Nisin Z, an antimicrobial peptide (AMP), can be considered an option, but its usage is mainly limited by the poor stability and short duration of its antimicrobial activity. In this context, cyclodextrin (CD)-based nanosponges (NSs), synthesized using carbonyldiimidazole (CDI) and pyromellitic dianhydride (PMDA), were chosen for nisin Z loading. To determine the minimum inhibitory of nisin Z loaded on CD-NS formulations, agar well diffusion plates were used. Then, the bactericide concentrations of nisin Z loaded on CD-NS formulations were determined against Gram-positive (Staphylococcus aureus) and -negative (Escherichia coli) bacteria, using microdilution brain heart infusion (BHI) and tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The minimum and bactericide inhibitory values o...
Advances in Nanostructures for Antimicrobial Therapy
Materials
Microbial infections caused by a variety of drug-resistant microorganisms are more common, but there are fewer and fewer approved new antimicrobial chemotherapeutics for systemic administration capable of acting against these resistant infectious pathogens. Formulation innovations of existing drugs are gaining prominence, while the application of nanotechnologies is a useful alternative for improving/increasing the effect of existing antimicrobial drugs. Nanomaterials represent one of the possible strategies to address this unfortunate situation. This review aims to summarize the most current results of nanoformulations of antibiotics and antibacterial active nanomaterials. Nanoformulations of antimicrobial peptides, synergistic combinations of antimicrobial-active agents with nitric oxide donors or combinations of small organic molecules or polymers with metals, metal oxides or metalloids are discussed as well. The mechanisms of actions of selected nanoformulations, including syste...
Nanotechnology-Based Delivery Systems for Antimicrobial Peptides
Pharmaceutics
Antimicrobial resistance (AMR) is a significant threat to global health. The conventional antibiotic pool has been depleted, forcing the investigation of novel and alternative antimicrobial strategies. Antimicrobial peptides (AMPs) have shown potential as alternative diagnostic and therapeutic agents in biomedical applications. To date, over 3000 AMPs have been identified, but only a fraction of these have been approved for clinical trials. Their clinical applications are limited to topical application due to their systemic toxicity, susceptibility to protease degradation, short half-life, and rapid renal clearance. To circumvent these challenges and improve AMP’s efficacy, different approaches such as peptide chemical modifications and the development of AMP delivery systems have been employed. Nanomaterials have been shown to improve the activity of antimicrobial drugs by providing support and synergistic effect against pathogenic microbes. This paper describes the role of nanotec...
Scientific Reports
Lantibiotics, bacteria-sourced antimicrobial peptides, are very good candidates for effective and safe food additives. Among them, nisin is already approved by the EU and FDA, and has been used in food preservation for the past 40 years. Now, there is a possibility and strong interest to extend its applicability to biomedicine for designing innovative alternatives to antibiotics. The main obstacle is, however, its naturally narrow spectrum of antimicrobial activity, focused on Gram positive bacteria. Here we demonstrate broadening nisin's spectrum to Gram negative bacteria using a nano-engineering approach. After binding nisin molecules to the surface of gold nano-features, uniformly deposited on spherical carbon templates, we created a nanocomposite with a high density of positively charged groups. Before assembly, none of the components of the nanocomposite showed any activity against bacterial growth, which was changed after assembly in the form of the nanocomposite. For the first time we showed that this type of structure enables interactions capable of disintegrating the wall of Gram negative bacteria. As confirmed by the nisin model, the developed approach opens up new horizons for the use of lantibiotics in designing post-antibiotic drugs.
Food Hydrocolloids, 2012
Customized application of antimicrobial peptide (AMP) 'nisin' directly into food (neither in active packaging nor encapsulated form) is expensive and associated with loss of activity due to deactivation in complex food systems. The purpose of the present study was to fusion the two concepts for improved bioavailability i.e. AMP nanoencapsulation and biopolymer immobilizing to formulate the next generation biodegradable films embedded with either active agent, nano-encapsulated active agent or both of them. Nanoliposomes were prepared using soy-lecithin by microfluidizer at 2000 bar with 5 cycles to generate an average size of 151 AE 4 nm with 50 AE 3% encapsulation efficiency. For active films, nisin had demonstrated no negative impact on transparency, thickness and water sorption behavior obtained by GAB model (25 C, 0e0.95 a w). For nano-active films, the results clearly illustrated that different physicochemical properties including barrier (oxygen and water vapor permeability), color and transparency (200e900 nm) remained comparable to native hydroxypropyl methylcellulose (HPMC) films and were significantly improved than using lecithin directly without nano-scale restructuring. The microstructure studies (topography and morphology) by scanning and transmission electron microscopes (SEM/TEM) revealed different (pore, lamellar, fusion) modes of nisin release from nanoliposomes embedded in HPMC matrix. As microbiological worth, nisin nano-emulsion (encapsulated and free nisin) films were effective against potential foodborne pathogen Listeria monocytogenes. This innovative concept of biodegradable nano-active films may thus be a preventive system toward improved food safety.
International Journal of Nanomedicine, 2017
Development of effective antibacterial agents for the treatment of infections caused by Gram-positive bacteria resistant to existing antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA), is an area of intensive research. In this work, the antibacterial efficacy of two antimicrobial peptides derived from plectasin, AP114 and AP138, used alone and in combination with monolaurin-lipid nanocapsules (ML-LNCs) was evaluated. Several interesting findings emerged from the present study. First, ML-LNCs and both plectasin derivatives showed potent activity against all 14 tested strains of S. aureus, independent of their resistance phenotype. Both peptides displayed a considerable adsorption (33%-62%) onto ML-LNCs without having an important impact on the particle properties such as size. The combinations of peptide with ML-LNC displayed synergistic effect against S. aureus, as confirmed by two methods: checkerboard and time-kill assays. This synergistic interaction enables a dose reduction and consequently decreases the risk of toxicity and has the potential of minimizing the development of resistance. Together, these results suggest that ML-LNCs loaded with a plectasin derivative may be a very promising drug delivery system for further development as a novel antibacterial agent against S. aureus, including MRSA.
Drug design, development and therapy, 2017
Conventional antibiotics are facing strong microbial resistance that has recently reached critical levels. This situation is leading to significantly reduced therapeutic potential of a huge proportion of antimicrobial agents currently used in clinical settings. Antimicrobial peptides (AMPs) could provide the medical community with an alternative strategy to traditional antibiotics for combating microbial resistance. However, the development of AMPs into clinically useful antibiotics is hampered by their relatively low stability, toxicity, and high manufacturing costs. In this study, a novel in-house-designed potent ultrashort AMP named RBRBR was encapsulated into chitosan-based nanoparticles (CS-NPs) based on the ionotropic gelation method. The encapsulation efficacy reported for RBRBR into CS-NPs was 51.33%, with a loading capacity of 10.17%. The release kinetics of RBRBR from the nanocarrier exhibited slow release followed by progressive linear release for 14 days. The antibacteri...