Hybrid Nanoparticles and Composite Hydrogel Systems for Delivery of Peptide Antibiotics

Abstract

The growing number of drug-resistant pathogenic bacteria poses a global threat to human health. For this reason, the search for ways to enhance the antibacterial activity of existing antibiotics is now an urgent medical task. The aim of this study was to develop novel delivery systems for polymyxins to improve their antimicrobial properties against various infections. For this, hybrid core–shell nanoparticles, consisting of silver core and a poly(glutamic acid) shell capable of polymyxin binding, were developed and carefully investigated. Characterization of the hybrid nanoparticles revealed a hydrodynamic diameter of approximately 100 nm and a negative electrokinetic potential. The nanoparticles demonstrated a lack of cytotoxicity, a low uptake by macrophages, and their own antimicrobial activity. Drug loading and loading efficacy were determined for both polymyxin B and E, and the maximal loaded value with an appropriate size of the delivery systems was 450 µg/mg of nanoparticles. Composite materials based on agarose hydrogel were prepared, containing both the loaded hybrid systems and free antibiotics. The features of polymyxin release from the hybrid nanoparticles and the composite materials were studied, and the mechanisms of release were analyzed using different theoretical models. The antibacterial activity against Pseudomonas aeruginosa was evaluated for both the polymyxin hybrid and the composite delivery systems. All tested samples inhibited bacterial growth. The minimal inhibitory concentrations of the polymyxin B hybrid delivery system demonstrated a synergistic effect when compared with either the antibiotic or the silver nanoparticles alone.

A pH/enzyme dual responsive PMB spatiotemporal release hydrogel promoting chronic wound repair

“…Recent research revealed that the hydrogel with biocompatibility, controllable modulus, and structure adjustable was considered as a promising the wound dressings for loading PMB [ 13 – 15 ]. In particular, the gelatin methacryloyl (GelMA), a semi-solid hydrogel, has received a great deal of attention owing to its biocompatibility, low immunogenicity, similarity to native tissue, and bio-degradability.…”

Polymyxin B Conjugates with Bio-Inspired Synthetic Polymers of Different Nature

“…In particular, three negatively charged polymers and a neutral glycopolymer were selected. Recently, copolymer of L-glutamic acid and L-phenylalanine (P(Glu-co-Phe)) [28] and poly(α,L-glutamic acid) (PGlu) [29] were tested as PMX B and E delivery systems, in which positively charged PMXs were bound to negatively charged polymers due to polyelectrolyte interactions. Here, PMX B was conjugated with P(Glu-co-Phe) and PGlu to compare the properties of physically loaded and covalently bound PMX B.…”

A pH/Enzyme Dual Responsive PMB Spatiotemporal Release Hydrogel Promoting Chronic Wound Repair

“…The research was focused on the antibacterial properties and biocompatibility of hydrogel to treat a full-thickness wound [14]. Some researchers were loading PMB into various hydrogels by entrapping mesh size and electrostatic interactions [18][19][20]. However, non-covalent encapsulation of PMB may allow for rapid release of the drug in the trabeculae, leading to instantaneous and extremely high local PMB concentrations triggering side effects.…”