Delivery Of Antimicrobial Peptides Research Articles

Nanostructures as Promising Tools for Delivery of Antimicrobial Peptides

Antimicrobial peptides have been extensively investigated for their potential applications as therapeutics and food biopreservatives. The antimicrobial activity may be impaired by the susceptibility for proteolytic degradation and undesirable interactions of the antimicrobial peptide in the biological environment. Development of nanostructures for entrapment and delivery of antimicrobial peptides may represent an alternative to the direct application of these substances. Lipid nanovesicles have been developed for encapsulation of antimicrobial peptides. Phosphatidylcholine is often employed in liposome manufacture, which is mostly achieved by the thin-film hydration method. Nanofibers may allow different physical modes of drug loading, including direct adsorption on the nanofiber surface or the assembly of drug-loaded nanoparticles. Self-assembled peptides reveal attractive features as nanostructures for applications in drug delivery and promising as antimicrobial agent for treatment of brain infections. Magnetic nanoparticles and nanotubules are also potential structures for entrapment of antimicrobial peptides. Nanoparticles can be also chemically modified with specific cell surface ligands to enhance cell adhesion and site specific delivery. This article reviews the most important nanostructures as promising tools for peptide delivery systems.

Local delivery of antimicrobial peptides using self‐organized TiO2 nanotube arrays for peri‐implant infections

Peri-implant infections have been reported as one of the major complications that lead to the failure of orthopedic implants. An ideal solution to the peri-implant infection is to locally deliver antimicrobial agents through the implant surface. The rising problem of infections caused by multiple antibiotic-resistant bacteria makes traditional antibiotics less desirable for the prevention of peri-implant infections. One of the promising alternatives is the family of antimicrobial peptides (AMPs). In this study, we report the local delivery of AMPs through the nanotubular structure processed on titanium surface. Self-organized and vertically oriented TiO2 nanotubes, about 80 nm in diameter and 7 μm thick, were prepared by the anodization technique. HHC-36 (KRWWKWWRR), one of the most potent broad-spectrum AMPs, was loaded onto the TiO2 nanotubes via a simple vacuum-assisted physical adsorption method. Antimicrobial activity testing against Gram-positive bacterium, Staphylococcus aureus, demonstrated that this AMP-loaded nanotubular surface could effectively kill the bacteria (≈ 99.9% killing) and reduce the total bacterial number adhered to the surface after 4 h of culture. In vitro AMP elution from the nanotubes was investigated using liquid chromatography-mass spectrometry (LC-MS). The release profiles strongly depended on the crystallinity of the TiO2 nanotubes. Anatase TiO2 nanotubes released significantly higher amounts of AMP than amorphous nanotubes during the initial burst release stage. Both followed almost the same slow release profile from 4 h up to 7 days. Despite the differences in release kinetics, no significant difference was observed between these two groups in bactericidal efficiency.

Macrophages Acquire Neutrophil Granules for Antimicrobial Activity against Intracellular Pathogens

A key target of many intracellular pathogens is the macrophage. Although macrophages can generate antimicrobial activity, neutrophils have been shown to have a key role in host defense, presumably by their preformed granules containing antimicrobial agents. Yet the mechanism by which neutrophils can mediate antimicrobial activity against intracellular pathogens such as Mycobacterium tuberculosis has been a long-standing enigma. We demonstrate that apoptotic neutrophils and purified granules inhibit the growth of extracellular mycobacteria. Phagocytosis of apoptotic neutrophils by macrophages results in decreased viability of intracellular M. tuberculosis. Concomitant with uptake of apoptotic neutrophils, granule contents traffic to early endosomes, and colocalize with mycobacteria. Uptake of purified granules alone decreased growth of intracellular mycobacteria. Therefore, the transfer of antimicrobial peptides from neutrophils to macrophages provides a cooperative defense strategy between innate immune cells against intracellular pathogens and may complement other pathways that involve delivery of antimicrobial peptides to macrophages.

Pexiganan‐incorporated collagen matrices for infected wound‐healing processes in rat

The use of peptide-based drugs is limited by their rapid degradability and toxicity at high concentration during their therapeutic application. These problems could be managed by the use of a peptide delivery agent for sustained release in the site of action. Collagen is one of the most proven biomaterials of good biocompatibility with an exceptional ligand encapsulating property. In this work, we have shown that pexiganan, an antimicrobial, 22-amino-acid peptide could be incorporated and delivered to the wound-healing site against bacterial strains Pseudomonas aeruginosa and Staphylococcus aureus. The release profiles of pexiganan collagen films with different collagen concentration were studied. The release of pexiganan from 2.5% w/w of collagen film showed a sustainable activity over 72 h with effective antimicrobial concentrations. Pexiganan-incorporated collagen (PIC)-treated groups were compared with open wound (OW)- and collagen film (CF)-treated rats. PIC-treated animals showed a diminishing level of bacterial growth as compared with OW- and CF-treated animals. The biochemical parameters such as hydroxyproline, protein, DNA, uronic acid, hexosamine, SOD, and catalase content in the granulation tissue of the healing wound revealed increased proliferation of cells involved in tissue reconstruction in PIC-treated groups when compared with OW- and CF-treated groups. Furthermore, spectroscopic studies suggested that collagen structure is not perturbed by pexiganan incorporation. This study provides rationale for application of collagen membrane for antimicrobial peptide delivery in infected wounds.