Porous Polymerized High Internal Phase Emulsions Prepared Using Proteins and Essential Oils for Antimicrobial Applications.

High internal phase emulsions (HIPEs) provide a versatile platform for encapsulating large volumes of therapeutics that are immiscible in water. A stable scaffold is obtained by polymerizing the external phase, resulting in polyHIPEs. However, fabrication of polyHIPEs usually requires using a considerable quantity of surfactants along with nonbiocompatible components, which hinders their biological applications, e.g., drug-eluting devices. We describe here a straightforward method for generating porous biomaterials by using proteins as both the emulsifier and the building blocks for the fabrication of polyHIPEs. We demonstrate the versatility of this method by using different essential oils as the internal phase. After the gelation of protein building blocks is triggered by the addition of reducing agents, a stable protein hydrogel containing essential oils can be formed. These oils can be either extracted to obtain protein-based porous scaffolds or slowly released for antimicrobial applications.

Biodegradable Antibacterial Bioorthogonal Polymeric Nanocatalysts Prepared by Flash Nanoprecipitation.

Bioorthogonal activation of pro-dyes and prodrugs using transition-metal catalysts (TMCs) provides a promising strategy for imaging and therapeutic applications. TMCs can be loaded into polymeric nanoparticles through hydrophobic encapsulation to generate polymeric nanocatalysts with enhanced solubility and stability. However, biomedical use of these nanostructures faces challenges due to unwanted tissue accumulation of nonbiodegradable nanomaterials and cytotoxicity of heavy-metal catalysts. We report here the creation of fully biodegradable nanocatalysts based on an engineered FDA-approved polymer and the naturally existing catalyst hemin. Stable nanocatalysts were generated through kinetic stabilization using flash nanoprecipitation. The therapeutic potential of these nanocatalysts was demonstrated through effective treatment of bacterial biofilms through the bioorthogonal activation of a pro-antibiotic.

Engineered Polymer-Supported Biorthogonal Nanocatalysts Using Flash Nanoprecipitation.

Transition-metal catalysts (TMCs) effect bioorthogonal transformations that enable the generation of therapeutic agents in situ, minimizing off-target effects. The encapsulation of insoluble TMCs into polymeric nanoparticles to generate "polyzymes" has vastly expanded their applicability in biological environments by enhancing catalyst solubility and stability. However, commonly used precipitation approaches provide limited encapsulation efficiency in polyzyme fabrication and result in a low catalytic activity. Herein, we report the creation of polyzymes with increased catalyst loading and optimized turnover efficiency using flash nanoprecipitation (FNP). Polyzymes with controlled size and catalyst loading were fabricated by tuning the process conditions of FNP. The biological applicability of polyzymes was demonstrated by efficiently transforming a non-toxic prodrug into the active drug within cancer cells.

Ultrasound-Enhanced Antibacterial Activity of Polymeric Nanoparticles for Eradicating Bacterial Biofilms.

Bacterial biofilms are a major healthcare concern resulting in refractory conditions such as chronic wounds, implant infections and failure, and multidrug-resistant infections. Aggressive and invasive strategies are employed to cure biofilm infections but are prone to long and expensive treatments, adverse side-effects, and low patient compliance. Recent strategies such as ultrasound-based therapies and antimicrobial nanomaterials have shown some promise in the effective eradication of biofilms. However, maximizing therapeutic effect while minimizing healthy tissue damage is a key challenge that needs to be addressed. Here a combination treatment involving ultrasound and antimicrobial polymeric nanoparticles (PNPs) that synergistically eradicate bacterial biofilms is reported. Ultrasound treatment rapidly disrupts biofilms and increases penetration of antimicrobial PNPs thereby enhancing their antimicrobial activity. This results in superior biofilm toxicity, while allowing for a two- to sixfold reduction in both the concentration of PNPs as well as the duration of ultrasound. Furthermore, that this reduction minimizes cytotoxicity toward fibroblast cells, while resulting in a 100- to 1000-fold reduction in bacterial concentration, is demonstrated.

Biodegradable Poly(lactic acid) Stabilized Nanoemulsions for the Treatment of Multidrug-Resistant Bacterial Biofilms.

Biofilm infections caused by multidrug-resistant (MDR) bacteria are an urgent global health threat. Incorporation of natural essential oils into biodegradable oil-in-water cross-linked polymeric nanoemulsions (X-NEs) provides effective eradication of MDR bacterial biofilms. The X-NE platform combines the degradability of functionalized poly(lactic acid) polymers with the antimicrobial activity of carvacrol (from oregano oil). These X-NEs exhibited effective penetration and killing of biofilms formed by pathogenic bacteria. Biofilm-fibroblast coculture models demonstrate that X-NEs selectively eliminate bacteria without harming mammalian cells, making them promising candidates for antibiofilm therapeutics.