Fast-Forming Dissolvable Redox-Responsive Hydrogels: Exploiting the Orthogonality of Thiol-Maleimide and Thiol-Disulfide Exchange Chemistry.

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 1H 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.

Biodegradable Nanocomposite Antimicrobials for the Eradication of Multidrug-Resistant Bacterial Biofilms without Accumulated Resistance.

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.

Theranostic nanogels: multifunctional agents for simultaneous therapeutic delivery and diagnostic imaging.

In recent years, there has been a growing interest in multifunctional theranostic agents capable of delivering therapeutic payloads while facilitating simultaneous diagnostic imaging of diseased sites. This approach offers a comprehensive strategy particularly valuable in dynamically evolving diseases like cancer, where combining therapy and diagnostics provides crucial insights for treatment planning. Nanoscale platforms, specifically nanogels, have emerged as promising candidates due to their stability, tunability, and multifunctionality as carriers. As a well-studied subgroup of soft polymeric nanoparticles, nanogels exhibit inherent advantages due to their size and chemical compositions, allowing for passive and active targeting of diseased tissues. Moreover, nanogels loaded with therapeutic and diagnostic agents can be designed to respond to specific stimuli at the disease site, enhancing their efficacy and specificity. This capability enables fine-tuning of theranostic platforms, garnering significant clinical interest as they can be tailored for personalized treatments. The ability to monitor tumor progression in response to treatment facilitates the adaptation of therapies according to individual patient responses, highlighting the importance of designing theranostic platforms to guide clinicians in making informed treatment decisions. Consequently, the integration of therapy and diagnostics using theranostic platforms continues to advance, offering intelligent solutions to address the challenges of complex diseases such as cancer. In this context, nanogels capable of delivering therapeutic payloads and simultaneously armed with diagnostic modalities have emerged as an attractive theranostic platform. This review focuses on advances made toward the fabrication and utilization of theranostic nanogels by highlighting examples from recent literature where their performances through a combination of therapeutic agents and imaging methods have been evaluated.

pH-Responsive nanofiber buttresses as local drug delivery devices.

Electrospun nanofibers are a 3D scaffold of choice for many drug delivery devices due to their high surface area, significant capacity for drug payload, ease of in situ placement, and scalable manufacture. Herein, we report the synthesis of polymeric, pH-responsive nanofiber buttresses via electrospinning. The homopolymer is comprised of an acrylic backbone with acid-sensitive, hydrolyzable, trimethoxybenzaldehyde-protected side chains that lead to buttress transformation from a hydrophobic to a hydrophilic state under physiologically relevant pH conditions (e.g., extracellular tumor environment with pH = 6.5). Hydrolysis of the side chains leads to an increase in fiber diameter from approximately 350 to 900 nm and the release of the encapsulated drug cargo. In vitro drug release profiles demonstrate that significantly more drug is released at pH 5.5 compared to pH 7.4, thereby limiting the release to the target site, with docetaxel releasing over 20 days and doxorubicin over 7 days. Drug burst release, defined as >50% within 24 hours, does not occur at either pH or with either drug. Drug-loaded buttresses preserve drug activity and are cytotoxic to multiple human cancer lines, including breast and lung. Important to their potential application in surgical applications, the tensile strength of the buttresses is 6.3 kPa and, though weaker than commercially available buttresses, they provide sufficient flexibility and mechanical integrity to serve as buttressing materials via the application with a conventional surgical cutting stapler.

Reduced Graphene-Oxide-Embedded Polymeric Nanofiber Mats: An "On-Demand" Photothermally Triggered Antibiotic Release Platform.

The steady increase of antimicrobial resistance of 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 allow 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 shows 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.