Enhancing the Activity of Surface Immobilized Antimicrobial Peptides Using Thiol-Mediated Tethering to Poly(ethylene glycol).

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol-mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol-mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two-step thiol-ene "photo-click" reaction or a "one-pot" thiol-maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG-AMP-modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol-mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections.

Highly active nisin coated polycaprolactone electrospun fibers against both Staphylococcus aureus and Pseudomonas aeruginosa.

In this study, a wound dressing of electrospun polycaprolactone (PCL) fibers incorporating the antimicrobial peptide (AMP) nisin was fabricated. Nisin was physically adsorbed to the PCL fibers and tested for antibacterial activity against both Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). The PCL fibers had an average diameter of 1.16 µm ± 0.42 µm and no significant change in diameter occurred after nisin adsorption. X-ray photoelectron spectroscopy (XPS) analysis of the fibers detected nitrogen indicative of adsorbed nisin and the signal was used to quantify the levels of coverage on the fiber surfaces. In vitro nisin release studies showed a burst release profile with 80 % of the nisin being released from the fibers within 30 min. Air plasma pre-treatment of the PCL fibers to render them hydrophilic improved nisin loading and release. Antibacterial testing was performed using minimum inhibitory concentration (MIC) and surface attachment assays. The released nisin remained active against both Gram positive S. aureus and Gram negative P. aeruginosa, which has previously been difficult to achieve with single polymer fiber systems. Mammalian cell culture of the nisin coated fibers with L-929 mouse fibroblasts and human epidermal keratinocytes (HEKa) showed that the nisin did not have a significant effect on the biocompatibility of the PCL fibers. The results presented here demonstrate that the physical adsorption, which is a post-treatment, overcomes the potential limitations of harsh chemicals and fabrication conditions of electrospinning from organic solvents and provides a drug loading system having effective antibacterial properties in wound dressings.

A nanofiber based antiviral (TAF) prodrug delivery system.

HIV and hepatitis B are two of the most prevalent viruses globally, and despite readily available preventive treatments unforgiving treatment regimens still exist, such as daily doses of medicine that are challenging to maintain especially in poorer countries. More advanced and longer-lasting delivery vehicles can potentially overcome this problem by reducing maintenance requirements and significantly increase access to medicine. Here, we designed a technology to control the delivery of an antiviral drug over a long timeframe via a nanofiber based delivery scaffold that is both easy to produce and use. An antiviral prodrug containing tenofovir alafenamide (TAF) was synthesized by initial conjugation to glycerol monomethacrylate followed by polymerization to form a diblock copolymer (pTAF) using reversible addition-fragmentation chain transfer (RAFT). In order to generate an efficient drug delivery system this copolymer was fabricated into an electrospun nanofiber (ESF) scaffold using blend electrospinning with poly(caprolactone) (PCL) as the carrier polymer. SEM images revealed that the pTAF-PCL ESFs were uniform with an average diameter of (787 ± 0.212 nm), while XPS analysis demonstrated that the pTAF was overrepresented at the surface of the ESFs. Additionally, the pTAF exhibited a sustained release profile over a 2 month period in human serum (HS), suggesting that these types of copolymer-based drugamers can be used in conjunction with electrospinning to produce long-lasting drug delivery systems.

Antimicrobial Peptide-Based Electrospun Fibers for Wound Healing Applications.

Current wound healing treatments such as bandages and gauzes predominantly rely on passively protecting the wound and do not offer properties that increase the rate of wound healing. While these strategies are strong at protecting any infection after application, they are ineffective at treating an already infected wound or assisting in tissue regeneration. Next-generation wound healing treatments are being developed at a rapid pace and have a variety of advantages over traditional treatments. Features such as gas exchange, moisture balance, active suppression of infection, and increased cell proliferation are all central to developing the next successful wound healing dressing. Electrospinning has already been shown to have the qualities required to be a key technique of next generation polymer-based wound healing treatments. Combined with antimicrobial peptides (AMPs), electrospun dressings can indeed become a formidable solution for the treatment of both acute and chronic wounds. The literature on combining electrospinning and AMPs is now starting to increase and this review aims to give a comprehensive overview of the current developments that combine electrospinning technology and AMPs in order to make multifunctional fibers effective against infection in wound healing.