Emerging Antimicrobial Research against Superbugs: Perspectives from a Polymer Laboratory

Infectious diseases caused by drug-resistant microorganisms have become a major contributor for human morbidity and mortality. To overcome such threats, we have developed various antimicrobial agents using natural product derivatives and metallopolymers. Abundant biomass such as resin acids can be utilized to prepare cationic polymers for inhibiting a variety of bacteria. These polymers have been used in solution as well as surfaces as antimicrobial materials with low cytotoxicity. In addition, a class of charged metallopolymers have been developed to kill superbugs such as MRSA

Lignin Biopolymers in the Age of Controlled Polymerization

Polymers made from natural biomass are gaining interest due to the rising environmental concerns and depletion of petrochemical resources. Lignin isolated from lignocellulosic biomass is the second most abundant natural polymer next to cellulose. The paper pulp process produces industrial lignin as a byproduct that is mostly used for energy and has less significant utility in materials applications. High abundance, rich chemical functionalities, CO2 neutrality, reinforcing properties, antioxidant and UV blocking abilities, as well as environmental friendliness, make lignin an interesting substrate for materials and chemical development. However, poor processability, low reactivity, and intrinsic structural heterogeneity limit lignins′ polymeric applications in high-performance advanced materials. With the advent of controlled polymerization methods such as ATRP, RAFT, and ADMET, there has been a great interest in academia and industry to make value-added polymeric materials from lignin. This review focuses on recent investigations that utilize controlled polymerization methods to generate novel lignin-based polymeric materials. Polymers developed from lignin-based monomers, various polymer grafting technologies, copolymer properties, and their applications are discussed

Macromolecular-Clustered Facial Amphiphilic Antimicrobials

Bacterial infections and antibiotic resistance, particularly by Gram-negative pathogens, have become a global healthcare crisis. We report the design of a class of cationic antimicrobial polymers that cluster local facial amphiphilicity from repeating units to enhance interactions with bacterial membranes without requiring a globally conformational arrangement associated with highly unfavorable entropic loss. This concept of macromolecular architectures is demonstrated with a series of multicyclic natural product-based cationic polymers. We have shown that cholic acid derivatives with three charged head groups are more potent and selective than lithocholic and deoxycholic counterparts, particularly against Gram-negative bacteria. This is ascribed to the formation of true facial amphiphilicity with hydrophilic ion groups oriented on one face and hydrophobic multicyclic hydrocarbon structures on the opposite face. Such local facial amphiphilicity is clustered via a flexible macromolecular backbone in a concerted way when in contact with bacterial membranes

Facially Amphiphilic Polyionene Biocidal Polymers Derived From Lithocholic Acid

Bacterial infections have become a global issue that requires urgent attention, particularly regarding to emergence of multidrug resistant bacteria. We developed quaternary amine-containing antimicrobial poly(bile acid)s that contain a hydrophobic core of lithocholic acid in the main-chain. Interestingly, by choosing appropriate monomers, these cationic polymers can form core-shell micelles. These polymers exhibited biocidal activity against both Gram-positive and Gram-negative bacterial species. It is demonstrated that the micelles can deliver hydrophobic antibiotics that functionally have dual antimicrobial activities. Cytotoxicity assays against HeLa cells showed dosage-dependent toxicity for polymers with longer linkers

Facially amphiphilic polyionene biocidal polymers derived from lithocholic acid

Bacterial infections have become a global issue that requires urgent attention, particularly regarding to emergence of multidrug resistant bacteria. We developed quaternary amine-containing antimicrobial poly(bile acid)s that contain a hydrophobic core of lithocholic acid in the main-chain. Interestingly, by choosing appropriate monomers, these cationic polymers can form core-shell micelles. These polymers exhibited biocidal activity against both Gram-positive and Gram-negative bacterial species. It is demonstrated that the micelles can deliver hydrophobic antibiotics that functionally have dual antimicrobial activities. Cytotoxicity assays against HeLa cells showed dosage-dependent toxicity for polymers with longer linkers

Highly swellable hydrogels prepared from extensively oxidized lignin

Biopolymers such as lignin are gaining renewed appeal due to the need for sustainable materials. Herein, we used chelator-mediated Fenton (CMF) chemistry to oxidize Kraft lignin to develop sustainable super absorbent materials. The CMF chemistry adds oxygen, opens aromatic rings and increases COOH content, producing hydrophilic lignin without depolymerization. UV absorption, molecular weight, elemental analysis, and titration were used to study the chemical compositions of CMF-processed lignin. Then the chemically modified hydrophilic lignin was used to produce lignin-based hydrogels utilizing an aqueous polymerization and cross-linking reaction that enabled tunable properties. The resulting lignin hydrogels absorbed water up to 96% and swelled up to 2400%, as well as being re-swellable in water. These lignin-based hydrogels may be applicable in water-absorbing products in consumer goods and agriculture

Physical Behavior of Triblock Copolymer Thermoplastic Elastomers Containing Sustainable Rosin-Derived Polymethacrylate End Blocks

A rosin-derived polymethacrylate, poly­(dehydroabietic ethyl methacrylate) (PDAEMA), was evaluated as a sustainable end block in triblock copolymer-based thermoplastic elastomers. Triblock copolymers containing glassy PDAEMA end blocks and a rubbery poly­(<i>n</i>-butyl acrylate) (PnBA) midblock were synthesized through atom transfer radical polymerization. The volume fraction of PDAEMA in the triblock copolymer was varied at constant midblock molecular weight. At lower PDAEMA content, the triblock copolymers exhibited microphase separated morphologies lacking long-range order, which transitioned to a well-defined cylindrical morphology as the PDAEMA content was increased. Observed thermal properties were consistent with the presence of distinct PDAEMA and PnBA domains. The order–disorder transition temperature increased with increasing PDAEMA content in the block copolymer, and the Flory–Huggins interaction parameter of PDAEMA/PnBA was strongly temperature-dependent yet small in value. The triblock copolymers exhibited elastomeric behavior at room temperature and accessible order–disorder transitions, appropriate for thermoplastic elastomer applications

Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity

Abstract Obesity is characterized by chronic low-grade, systemic inflammation, altered gut microbiota, and gut barrier disruption. Additionally, obesity is associated with increased activity of endocannabinoid system (eCB). However, the clear connection between gut microbiota and the eCB system in the regulation of energy homeostasis and adipose tissue inflammation and metabolism, remains to be established. We investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment that blocks endocannabinoid activity can induce changes in gut microbiota and anti-inflammatory state in adipose tissue. Blockade of CB1 attenuated DIO, inflammatory cytokines and trafficking of M1 macrophages into adipose tissue. Decreased inflammatory tone was associated with a lower intestinal permeability and decreased metabolic endotoxemia as evidenced by reduced plasma LPS level, and improved hyperglycemia and insulin resistance. 16S rRNA metagenomics sequencing revealed that CB1 blockade dramatically increased relative abundance of Akkermansia muciniphila and decreased Lanchnospiraceae and Erysipelotrichaceae in the gut. Together, the current study suggests that blocking of CB1 ameliorates Diet-Induced Obesity and metabolic disorder by modulating macrophage inflammatory mediators, and that this effect is associated with alterations in gut microbiota and their metabolites