The steady increase in antimicrobial resistance in different pathogens requires the development of alternative treatment strategies next to the oral delivery of antibiotics. A photothermally activated platform based on reduced graphene oxide (rGO)-embedded polymeric nanofiber mats for on-demand release of antibiotics upon irradiation in the near-infrared is fabricated. Cross-linked hydrophilic nanofibers, obtained by electrospinning a mixture of poly(acrylic acid) (PAA) and rGO, show excellent stability in aqueous media. Importantly, these PAA@ rGO nanofiber mats exhibit controlled photothermal heating upon irradiation at 980 nm. Nanofiber mats are efficiently loaded with antibiotics through simple immersion into corresponding antibiotics solutions. Whereas passive diffusion based release at room temperature is extremely low, photothermal activation results in increased release within few minutes, with release rates tunable through power density of the applied irradiation. The large difference over passive and active release, as well as the controlled turn-on of release allows regulation of the dosage of the antibiotics, as evidenced by the inhibition of planktonic bacteria growth. Treatment of superficial skin infections with the antibiotic-loaded nanofiber mats show efficient wound healing of the infected site. Facile fabrication and implementation of these photothermally active nanofiber mats makes this novel platform adaptable for on-demand delivery of various therapeutic agents.
Infections caused by bacterial biofilms are an emerging threat to human health. Conventional antibiotic therapies are ineffective against biofilms due to poor penetration of the extracellular polymeric substance (EPS) secreted by colonized bacteria, coupled with the rapidly growing number of antibiotic-resistant strains. Essential oils are promising natural antimicrobial agents, however poor solubility in biological conditions limits their applications against bacteria in both dispersed (planktonic) and biofilm settings. We report here an oil-in-water crosslinked polymeric nanocomposite (~250 nm) incorporating carvacrol oil that penetrates and eradicates multidrug-resistant (MDR) biofilms. The therapeutic potential of these materials against challenging wound biofilm infections was demonstrated through specific killing of bacteria in a mammalian cell - biofilm co-culture wound model.
In recent years, stimuli-responsive degradation has emerged as a desirable design criterion for functional hydrogels to tune the release of encapsulated payload as well as ensure degradation of the gel upon completion of its function. Herein, redox-responsive hydrogels with a well-defined network structure were obtained using a highly efficient thiol-disulfide exchange reaction. In particular, gelation occurred upon combining thiolterminated tetra-arm polyethylene glycol (PEG) polymers with linear telechelic PEG-based polymers containing pyridyl disulfide units at their chain ends. Rapid gelation proceeds with good conversions (>85%) to yield macroporous hydrogels possessing high water uptake. Furthermore, due to the presence of the disulfide linkages, the thus-obtained hydrogels can self-heal. The obtained hydrogels undergo complete degradation when exposed to environments rich in thiol-containing agents such as dithiothreitol (DTT) and L-glutathione (GSH). Also, the release profile of encapsulated protein, namely, bovine serum albumin, can be tuned by varying the molecular weight of the polymeric precursors. Additionally, it was demonstrated that complete dissolution of the hydrogel to rapidly release the encapsulated protein occurs upon treating these hydrogels with DTT. Cytotoxicity evaluation of the hydrogels and their degradation products indicated the benign nature of these hydrogels. Additionally, the cytocompatible nature of these materials was also evident from a live/dead cell viability assay. One can envision that the facile fabrication and their ability to degrade on-demand and release their payload will make these benign polymeric scaffolds attractive for various biomedical applications.
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