Infections caused by multidrug-resistant (MDR) bacteria are a rapidly growing threat to human health, in many cases exacerbated by their presence in biofilms. We report here a biocompatible oil-in-water cross-linked polymeric nanocomposite that degrades in the presence of physiologically relevant biomolecules. These degradable nanocomposites demonstrated broad-spectrum penetration and elimination of MDR bacteria, eliminating biofilms with no toxicity to cocultured mammalian fibroblast cells. Notably, serial passaging revealed that bacteria were unable to develop resistance toward these nanocomposites, highlighting the therapeutic promise of this platform.
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.
This review provides an overview of synthetic approaches utilized to incorporate the thiol-reactive pyridyl-disulfide motif into various polymeric materials, and briefly highlights its utilization to obtain functional materials.
Poly(ethylene glycol)-based redox-responsive hydrogels have been prepared via the Diels–Alder reaction between a furan-containing hydrophilic copolymer and a disulfide-containing bis-maleimide based crosslinker.
Fast-forming yet
easily dissolvable hydrogels (HGs) have potential
applications in wound healing, burn incidences, and delivery of therapeutic
agents. Herein, a combination of a thiol–maleimide conjugation
and thiol–disulfide exchange reaction is employed to fabricate
fast-forming HGs which rapidly dissolve upon exposure to dithiothreitol
(DTT), a nontoxic thiol-containing hydrophilic molecule. In particular,
maleimide disulfide-terminated telechelic linear poly(ethylene glycol)
(PEG) polymer and PEG-based tetrathiol macromonomers are employed
as gel precursors, which upon mixing yield HGs within a minute. The
selectivity of the thiol–maleimide conjugation in the presence
of a disulfide linkage was established through
1
H NMR spectroscopy
and Ellman’s test. Rapid degradation of HGs in the presence
of thiol-containing solution was evident from the reduction in storage
modulus. HGs encapsulated with fluorescent dye-labeled dextran polymers
and bovine serum albumin were fabricated, and their cargo release
was investigated under passive and active conditions upon exposure
to DTT. One can envision that the rapid gelation and fast on-demand
dissolution under relatively benign conditions would make these polymeric
materials attractive for a range of biomedical applications.
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