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Hydrogels pharmacology, Alginates pharmacology, Wound Healing, Polymers pharmacology, Curcumin pharmacology, Curcumin therapeutic use, and Neoplasms

Hydrogels have emerged as a versatile platform for a numerous biomedical application due to their ability to absorb a huge quantity of biofluids. In order to design hydrogels, natural polymers are an attractive option owing to their biocompatibility and biodegradability. Due to abundance in occurrence, cost effectiveness, and facile crosslinking approaches, alginate has been extensively investigated to fabricate hydrogel matrix. Management of cancer and chronic wounds have always been a challenge for pharmaceutical and healthcare sector. In both cases, curcumin have been shown significant improvement and effectiveness. However, the innate restraints like poor bioavailability, hydrophobicity, and rapid systemic clearance associated with curcumin have restricted its clinical translations. The current review explores the cascade of research around curcumin encapsulated alginate hydrogel matrix for wound healing and cancer therapy. The focus of the review is to emphasize the mechanistic effects of curcumin with its fate inside the cells. Further, the review discusses different approaches to designed curcumin loaded alginate hydrogels along with the parameters that regulates their release behavior. Finally, the review is concluded with emphasize on some key aspect on increasing the efficacy of these hydrogels along with novel strategies to further develop curcumin loaded alginate hydrogel matrix with multifacet applications.
Competing Interests: Conflict of interest The authors declare no conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Humans, Quercetin pharmacology, Polymers pharmacology, Molecular Docking Simulation, Drug Resistance, Neoplasm, Doxorubicin pharmacology, Doxorubicin chemistry, Drug Resistance, Multiple, ATP Binding Cassette Transporter, Subfamily B, MCF-7 Cells, Cell Line, Tumor, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Antineoplastic Agents pharmacology, and Antineoplastic Agents chemistry

In this study, we prepared a β-cyclodextrin polymer (β-CDP) co-loaded quercetin (QCT) and doxorubicin (DOX) nanocarrier (β-CDP/QD NCs) by freeze-dried method to combat P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in KB-Ch R 8-5 cancer cells. Various microscopic and spectroscopic techniques were employed to characterize the prepared nanocarrier. The molecular docking studies confirm the effective binding interactions of QCT and DOX with the synthesized β-CD polymer. The in vitro drug release study illustrates the sustainable release of DOX and QCT from the β-CDP nanocarrier. Further, we noticed that the QCT released from the β-CDP nanocarrier improved the intracellular availability of DOX via modulating P-gp drug efflux function in KB-Ch R 8-5 cells and MCF-7/DOX cancer cells. Cell uptake results confirmed the successful internalization of DOX in KB-Ch R 8-5 cells compared with free DOX. Cell-based assays such as nuclear condensation, alteration in the mitochondrial membrane potential (MMP), and apoptosis morphological changes confirmed the enhanced anticancer effect of β-CDP/QD NCs in the resistant cancer cells. Hence, QCT and DOX co-loaded β-CDP may be considered effective in achieving maximum cell death in the P-gp overexpressing MDR cancer cells.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)

Photothermal Therapy, Phototherapy, Polymers pharmacology, Escherichia coli, Staphylococcus aureus, Nanoparticles, and Anti-Infective Agents

A novel donor (D)-acceptor (A) structured conjugated polymer (PDPP-TP), which contains two alternating D-A pairs, namely thiophene (T)-diketopyrrolopyrrole (DPP) and thiophenen (T)-thieno[3,4- b ]pyrazine (TP) along the main chain of the polymer, was synthesized by direct arylation polycondensation (DArP) for a highly efficient photothermal antibacterial treatment. The hydrophilic PDPP-TP-based nanoparticles (PTNPs) with a hydration diameter of about 120 nm were obtained by self-assembly using DSPE-mPEG 2000 as the polymer matrix. PTNPs show strong near-infrared (NIR) absorbance with a λ max at 910 nm ( ε = 2.25 × 10 4 L mol -1 cm -1 ) and NIR light-triggered photoactivity with a high photothermal conversion efficiency (PTCE) of 52.8% under 880 nm laser irradiation. Keeping the merits of excellent biocompatibility and photostability, PTNPs exhibited remarkable bacterial inhibition efficiency of almost 100% against Gram-negative E. coli and Gram-positive S. aureus with the help of an 880 nm laser (0.7 W cm -2 , 6 min), demonstrating its great potential as photothermal materials with a broad spectrum of activity for the effective treatment of microbial infections.

Animals, Mice, Carcinogenesis, Cell Proliferation, Micelles, Mutation, Polymers pharmacology, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Proto-Oncogene Proteins p21(ras) pharmacology, Intracellular Space, Colorectal Neoplasms pathology, and Neoplasms

The Kirsten rat sarcoma viral oncogene (KRAS) is one of the most well-known proto-oncogenes, frequently mutated in pancreatic and colorectal cancers, among others. We hypothesized that the intracellular delivery of anti-KRAS antibodies (KRAS-Ab) with biodegradable polymeric micelles (PM) would block the overactivation of the KRAS-associated cascades and revert the effect of its mutation. To this end, PM-containing KRAS-Ab (PM-KRAS) were obtained using Pluronic F127. The feasibility of using PM for antibody encapsulation as well as the conformational change of the polymer and its intermolecular interactions with the antibodies was studied, for the first time, using in silico modeling. In vitro , encapsulation of KRAS-Ab allowed their intracellular delivery in different pancreatic and colorectal cancer cell lines. Interestingly, PM-KRAS promoted a high proliferation impairment in regular cultures of KRAS-mutated HCT116 and MIA PaCa-2 cells, whereas the effect was neglectable in non-mutated or KRAS-independent HCT-8 and PANC-1 cancer cells, respectively. Additionally, PM-KRAS induced a remarkable inhibition of the colony formation ability in low-attachment conditions in KRAS-mutated cells. In vivo, when compared with the vehicle, the intravenous administration of PM-KRAS significantly reduced tumor volume growth in HCT116 subcutaneous tumor-bearing mice. Analysis of the KRAS-mediated cascade in cell cultures and tumor samples showed that the effect of PM-KRAS was mediated by a significant reduction of the ERK phosphorylation and a decrease in expression in the stemness-related genes. Altogether, these results unprecedently demonstrate that the delivery of KRAS-Ab mediated by PM can safely and effectively reduce the tumorigenicity and the stemness properties of KRAS-dependent cells, thus bringing up new possibilities to reach undruggable intracellular targets.

Humans, Humidity, Polymers pharmacology, Staphylococcus aureus, Escherichia coli, Ionic Liquids pharmacology, and Anti-Infective Agents pharmacology

Humidity-responsive materials have attracted increasing attention for their potential use in various applications, e.g., sensors, soft robotics, and human-machine interfaces. Much effort has been focused on the use of ionic liquids for the construction of humidity-responsive sensors; yet, not enough attention has been paid on the susceptibility of the used poly(ionic liquid)s to microorganisms. This is especially relevant to the wide use of the polymers for biomedical applications, e.g., wearable body-condition sensors or healthcare control systems. We herein describe the development of dual functional, self-standing, monolayer antimicrobial membranes derived from cross-linked copolymers functionalized with ionic liquids. In a first step, random copolymers of poly(4-vinylbenzyl N -alkyl imidazolium chloride- co -acrylic acid), P(VBCImC n - co -AA20), were synthesized bearing aliphatic chains of different lengths (where n = 1, 4, 8, 12, 16 carbon atoms) to investigate the effect of hydrophobicity/hydrophilicity on the humidity-responsive properties of the copolymer and its antimicrobial activity. The aforementioned copolymers were later blended with the complementary reactive copolymers of poly(cetyl trimethylammonium 4-styrene sulfonate- co -glycidyl methacrylate), P(SSAmC 16 - co -GMA20), to provide highly stable films and coatings through thermal cross-linking. The membrane P(VBCImC 12 - co -AA20)/P(SSAmC 16 - co -GMA20) with a molar ratio of 3:1 (mol AA/mol GMA) exhibited immediate and high response to moisture through folding or flipping motions when placed on a wet filter paper or on the palm of a hand. The inhibition of growth for selected bacterial species ( Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus aureus ) on the copolymer membranes was dependent on the length of the imidazolium alkyl chain and the species. Additionally, in the case of the cross-linked P(VBCImC n - co -AA20)/P(SSAmC 16 - co -GMA20) membranes, the overall efficacy was very high against all microorganisms tested, which, combined with their high humidity responsiveness, enables their potential application.

Humans, Polymers pharmacology, Fluorescent Dyes, Candida albicans, Antifungal Agents pharmacology, and Itraconazole pharmacology

The therapy of life-threatening fungal infections is limited and needs urgent improvement. This is in part due to toxic side effects of clinically used antifungal compounds or their limited delivery to fungal structures. Until today, it is a matter of debate how drugs or drug-delivery systems can efficiently reach the intracellular lumen of fungal cells and how this can be improved. Here, we addressed both questions by applying two different polymeric particles for delivery of compounds. Their formulation was based on two biocompatible polymers, i.e., poly(lactic-co-glycolic acid) 50:50 and poly(methyl methacrylate-stat-methacrylic acid) 90:10 yielding particles with hydrodynamic diameters ranging from 100 to 300 nm. The polymers were covalently labeled with the fluorescent dye DY-550 to monitor the interaction between particles and fungi by confocal laser scanning microscopy. Furthermore, the fluorescent dye coumarin-6 and the antifungal drug itraconazole were successfully encapsulated in particles to study the fate of both the cargo and the particle when interacting with the clinically most important human-pathogenic fungi Aspergillus fumigatus, A. terreus, Candida albicans, and Cryptococcus neoformans. While the polymers were exclusively located on the fungal surface, the encapsulated cargo was efficiently transported into fungal hyphae, indicated by increased intracellular fluorescence signals due to coumarin-6. In accordance with this finding, compared to the pristine drug a reduced minimal inhibitory concentration for itraconazole was determined, when it was encapsulated. Together, the herein used polymeric particles were not internalized by pathogenic fungi but were able to efficiently deliver hydrophobic cargos into fungal cells.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)

Reproducibility of Results, Drug Liberation, Polymers pharmacology, Hydrogen-Ion Concentration, Drug Carriers pharmacology, Trypanosoma cruzi, Anacardium, and Nanoparticles chemistry

Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.
Competing Interests: Declaration of competing interest The authors have no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)

Polymers pharmacology, Endothelial Cells, and Dopamine

Dopamine is a small molecule inspired by the dopamine motif of mussel foot proteins, and PDA is formed by the self-polymerization of dopamine. Under the UV-irradiation，PDA would be oxidized by reactive oxygen species (ROS) which were produced by photocatalytic reactions on TiO 2 surfaces，thus regulating the adhesion behavior of endothelial cells (ECs) TiO 2 inhibited platelet (Plt) adhesion after UV exposure. Polydopamine (PDA)-TiO 2 micropatterns (P-PDA-TiO 2 ) were prepared by magnetron sputtering and photolithography. This micropatterns successfully achieves selective adhesion of Plt and ECs. The selective adhesion of ECs disappears after vacuum reduction. In contrast to conventional cell patterning strategies, P-PDA-TiO 2 can easily achieve pattern separation of ECs and Plts and provide a new concept for building complex blood-contacting devices.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)

Humans, Cell Survival, Drug Delivery Systems, Polymers pharmacology, Polymers chemistry, Dopamine pharmacology, and Neuroblastoma

Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the capability to make the entrapped drug molecule amorphous, which increases bioavailability. By covalently conjugating drugs onto polymers, the degradation of the drug as well as the fast clearance from the circulation can be avoided. Although covalent polymer-drug conjugates have a lot of advantages, there is a lack of research focusing on their nano-formulation by electrospinning. In this study, polysuccinimide (PSI) based electrospun fibrous meshes conjugated with dopamine (DA) are prepared. Fiber diameter, mechanical properties, dissolution kinetics and membrane permeability are thoroughly investigated, as these are crucial for drug delivery and implantation. Dopamine release kinetics prove the prolonged release that influenced the viability and morphology of periodontal ligament stem cells (PDLSCs) and SH-SY5Y cells. The presence of dopamine receptors on both cell types is also demonstrated and the uptake of the conjugates is measured. According to flow cytometry analysis, the conjugates are internalized by both cell types, which is influenced by the chemical structure and physical properties. In conclusion, electrospinning of PSI-DA conjugates alters release kinetics, meanwhile, conjugated dopamine can play a key role in cellular uptake.
(© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

Polymers pharmacology, Silicon Dioxide, Biofilms, and Methacrylates pharmacology

Introduction: The number of published biofilm studies and novel ways for studying them has risen dramatically in recent years, ow-ing to the broad application of biofilms in medicine. Some bacteria develop biofilms that are highly resistant to antimicrobial agents, resulting in persistent infections. This necessitates the development of alternative methods for combating biofilms. In this regard, the application of cationic polymers is a good candidate for realization of this strategy.
Aim: The aim of our study was to investigate the potential of a newly synthesized covalently attached star copolymer of N,N'-dimeth-ylaminoethyl methacrylate and hydroxyl-bearing oligo(ethylene glycol) methacrylate [P(DMAEMA-co-HOEGMA)] to silica surfaces and its quaternized version [P(QDMAEMA-co-HOEGMA)] for destruction of biofilms formed by Bacillus subtilis or Pseudomonas aeruginosa.
Materials and Methods: Model strains representing different genera and taxonomic groups were selected for the study. The anti-biofilm activities of two different newly synthesized cationic polymers were investigated by observation (live/dead staining) of the viability of bacterial cells within the biofilm.
Results: The results obtained by the live/dead labeling of bacterial biofilms show a substantial decrease in the viability of population in the presence of cationic polymers, better expressed at B. subtilis.
Conclusions: The studied two immobilized on silica wafers newly synthesized star copolymers exhibited potential for anti-biofilm effects. The results demonstrated combined potential for reducing the viability of bacterial cells within the biofilms and probably for loosening the biofilm matrix. The effect was better expressed in B. subtilis.
(This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Animals, Mice, Cysteine, Polymers pharmacology, Paclitaxel pharmacology, Paclitaxel therapeutic use, Oxidation-Reduction, Ferroptosis, and Leukemia, Myeloid, Acute drug therapy

Ferroptosis is an alternative strategy to overcome chemoresistance, but effective therapeutic approaches to induce ferroptosis for acute myeloid leukemia (AML) treatment are limited. Here, we developed glutathione (GSH)-responsive cysteine polymer-based ferroptosis-inducing nanomedicine (GCFN) as an efficient ferroptosis inducer and chemotherapeutic drug nanocarrier for AML treatment. GCFN depleted intracellular GSH and inhibited glutathione peroxidase 4, a GSH-dependent hydroperoxidase, to cause lipid peroxidation and ferroptosis in AML cells. Furthermore, GCFN-loaded paclitaxel (PTX@GCFN) targeted AML cells and spared normal hematopoietic cells to limit the myeloablation side effects caused by paclitaxel. PTX@GCFN treatment extended the survival of AML mice by specifically releasing paclitaxel and simultaneously inducing ferroptosis in AML cells with restricted myeloablation and tissue damage side effects. Overall, the dual-functional GCFN acts as an effective ferroptosis inducer and a chemotherapeutic drug carrier for AML treatment.

Animals, Chickens, Micelles, Spectroscopy, Fourier Transform Infrared, Polymers pharmacology, Eimeria tenella, Coccidiostats pharmacology, Coccidiostats therapeutic use, Poultry Diseases drug therapy, Poultry Diseases prevention control, Coccidiosis drug therapy, Coccidiosis veterinary, and Coccidiosis epidemiology

Coccidiosis is a worldwide epidemic intestinal disease with high incidence, which causes huge economic losses. Halofuginone hydrobromide (HF) is widely applied as an effective anticoccidial drug in the poultry industry. However, its therapeutic efficacy is severely restrained due to toxic effects, poor aqueous solubility and low permeability. Nanotechnology can improve the biological effect of drugs, and thus, reduce administered doses and toxic effects. The objective of this study was to investigate the therapeutic and preventive potential of novel HF-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) polymer micelles (HTPM) for preventing coccidiosis in chickens. The HTPM were approximately spherical with a hydrodynamic diameter of 12.65 ± 0.089 nm, a zeta potential of 8.03 ± 0.242 mV, a drug loading of 14.04 ± 0.12%, and an encapsulation efficiency of 71.1 ± 4.15%. HF was encapsulated in the polymer micelles through interactions with TPGS, as characterized by X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy. Cellular take up assays showed that TPGS polymer micelles could enhance drug internalization to alleviate intestinal apoptosis induced by coccidiosis and promote the necrosis of second-generation merozoites of E. tenella . Notably, clinical trials proved that 1.5 mg L -1 HTPM had a stronger anticoccidial effect on E. tenella than that of 3 mg kg -1 HF premix. Amplicon sequencing identified that HTPM could alleviate coccidiosis by restoring the structure of the gut microbiome. These findings indicated that the anticoccidial efficacy of HF was significantly enhanced after being encapsulated in polymer micelles, and further demonstrated the potential protective application of nano-encapsulating anticoccidial drugs as a promising approach to control coccidiosis in poultry. In summary, HTPM hold huge potential as an effective therapeutic agent for coccidiosis.

Polymers pharmacology, Lignin pharmacology, Pyrroles, Endotoxins pharmacology, Sodium pharmacology, Escherichia coli, Staphylococcus aureus, Adsorption, Anti-Bacterial Agents pharmacology, and Chitosan pharmacology

There is an urgent need to develop materials to prevent bacterial infection and the deleterious effects of endotoxins. In this study, we introduce a one-step electrodeposition method to prepare films composed of chitosan/Ag/polypyrrole and layer-by-layer self-assembly to introduce lignin sulphonate (LS) to obtain chitosan/Ag/polypyrrole/LS films. Antibacterial effects against both E. coli and S. aureus are shown by bacterial growth profiles and observation of bacteriostatic zones. Meanwhile, the addition of self-assembled LS improved the antibacterial effect of the film. For E. coli, the inhibition zone diameter was 0.93 cm, while for S. aureus, the inhibition zone diameter was 0.72 cm. Rapid and efficient endotoxin adsorption effects were shown whereby the electrostatic interactions between chitosan and endotoxin molecules played a major role. After adsorption for 1 h, in initial concentration of 1 EU/mL endotoxin solution, the adsorption efficiency could reach up to 85 %, while in initial concentration of 5 EU/mL endotoxin solution, the adsorption efficiency could reach up to 87.6 %. The results suggest chitosan/Ag/polypyrrole/LS films for their capability as a new type of antibacterial film with intrinsic endotoxin adsorption activity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022. Published by Elsevier B.V.)

Gram-Negative Bacteria, Gram-Positive Bacteria, Bacteria, Polymers pharmacology, Polymers chemistry, Microbial Sensitivity Tests, Anti-Bacterial Agents chemistry, and Anti-Infective Agents pharmacology

Antimicrobial resistance is a global challenge owing to the lack of discovering effective antibiotic agents. Antimicrobial polymers containing the cationic groups and hydrophobic groups which mimic natural host-defense peptides (HDPs) show great promise in combating bacteria. Herein, we report the synthesis of lipidated polycarbonates bearing primary amino groups and hydrophobic moieties (including both the terminal long alkyl chain and hydrophobic groups in the sequences) by ring-opening polymerization. The hydrophobic/hydrophilic group ratios were adjusted deliberately and the lengths of the alkyl chains at the end of the polymers were modified to achieve the optimized combination for the lead polymers, which exhibited potent and broad-spectrum bactericidal activity against a panel of Gram-positive and Gram-negative bacteria. The polymers only showed very limited hemolytic activity, demonstrating their excellent selectivity. Comprehensive analyses using biochemical and biophysical assays revealed the strong interaction between the polymers and bacteria membranes. Moreover, the polymers also showed strong biofilm inhibition activity and did not readily induce antibiotic resistance. Our results suggest that lipidated polycarbonates could be a new class of antimicrobial agents.

Humans, Flavonoids pharmacology, Colon, Polymers pharmacology, Inflammatory Bowel Diseases drug therapy, and Nanoparticles

Inflammatory bowel disease (IBD) is a group of disorders that cause chronic non-specific inflammation in the gastrointestinal (GI) tract, primarily affecting the ileum and colon. The incidence of IBD has risen sharply in recent years. Despite continuous research efforts over the past decades, the aetiology of IBD is still not fully understood and only a limited number of drugs are available for its treatment. Flavonoids, a ubiquitous class of natural chemicals found in plants, have been widely used in the prevention and treatment of IBD. However, their therapeutic efficacy is unsatisfactory due to poor solubility, instability, rapid metabolism, and rapid systemic elimination. With the development of nanomedicine, nanocarriers can efficiently encapsulate various flavonoids and subsequently form nanoparticles (NPs), which greatly improves the stability and bioavailability of flavonoids. Recently, progress has also been made in the methodology of biodegradable polymers that can be used to fabricate NPs. As a result, NPs can significantly enhance the preventive or therapeutic effects of flavonoids on IBD. In this review, we aim to evaluate the therapeutic effect of flavonoid NPs on IBD. Furthermore, we discuss possible challenges and future perspectives.

Escherichia coli, Methylmethacrylate, Staphylococcus aureus, Methacrylates pharmacology, Polymers pharmacology, Anti-Bacterial Agents pharmacology, Photosensitizing Agents pharmacology, Anti-Infective Agents pharmacology, and Photochemotherapy

In this work, two compounds belonging to the BODIPY family, and previously investigated for their photosensitizing properties, have been bound to the amino-pendant groups of three random copolymers, with different amounts of methyl methacrylate (MMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) in the backbone. The P(MMA- ran -DMAEMA) copolymers have inherently bactericidal activity, due to the amino groups of DMAEMA and to the quaternized nitrogens bounded to BODIPY. Systems consisting of filter paper discs coated with copolymers conjugated to BODIPY were tested on two model microorganisms, Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). On solid medium, irradiation with green light induced an antimicrobial effect, visible as a clear inhibition area around the coated disks. The system based on the copolymer with 43% DMAEMA and circa 0.70 wt/wt% of BODIPY was the most efficient in both bacterial species, and a selectivity for the Gram-positive model was observed, independently of the conjugated BODIPY. A residual antimicrobial activity was also observed after dark incubation, attributed to the inherently bactericidal properties of copolymers.

Escherichia coli, Anti-Bacterial Agents pharmacology, Cations chemistry, Polymers pharmacology, and Anti-Infective Agents pharmacology

The performance of antimicrobial polymers depends sensitively on the type of cationic species, charge density, and spatial arrangement of cations. Here we report antimicrobial polymers bearing unusually bulky tetraaminophosphonium groups as the source of highly delocalized cationic charge. The bulky cations drastically enhanced the biocidal activity of amphiphilic polymers, leading to remarkably potent activity in the submicromolar range. The cationic polynorbornenes with pendent tetraaminophosphonium groups killed over 98% E. coli at a concentration of 0.1 μg/mL and caused a 4-log reduction of E. coli within 2 h at a concentration of 2 μg/mL, showing very rapid and potent bactericidal activity. The polymers are also highly hemolytic at similar concentrations, indicating a biocidal activity profile. Polymers of a similar chemical structure but with more flexible backbones were made to examine the effects of the flexibility of polymer chains on their activity, which turned out to be marginal. We also explore variants with different spacer arm groups separating the cations from the backbone main chain. The antibacterial activity was comparably potent in all cases, but the polymers with shorter spacer arm groups showed more rapid bactericidal kinetics. Interestingly, pronounced counterion effects were observed. Tightly bound PF 6 - counteranions showed poor activity at high concentrations due to gross aggregate formation and precipitation from the assay media, whereas loosely bound Cl - counterions resulted in very potent activity that monotonically increased with increasing concentration. In this paper, we reveal that bulky phosphonium cations are associated with markedly enhanced biocidal activity, which provides an innovative strategy to develop more effective self-disinfecting materials.

Animals, Male, Microplastics toxicity, Plastics, Polymers pharmacology, Polymethyl Methacrylate pharmacology, Semen, Sea Urchins, Embryonic Development, Arbacia, Insecticides pharmacology, Water Pollutants, Chemical toxicity, and Pyrethrins pharmacology

As a proxy for pollutants that may be simultaneously present in urban wastewater streams, the effects of two microplastics-polystyrene (PS; 10, 80 and 230 μm diameter) and polymethylmethacrylate (PMMA; 10 and 50 μm diameter)-on fertilisation and embryogenesis in the sea urchin Arbacia lixula with co-exposure to the pyrethroid insecticide cypermethrin were investigated. Synergistic or additive effects were not seen for plastic microparticles (50 mg L -1 ) in combination with cypermethrin (10 and 1000 μg L -1 ) based on evaluation of skeletal abnormalities or arrested development and death of significant numbers of larvae during the embryotoxicity assay. This behaviour was also apparent for male gametes pretreated with PS and PMMA microplastics and cypermethrin, where a reduction in sperm fertilisation ability was not evidenced. However, a modest reduction in the quality of the offspring was noted, suggesting that there may be some transmissible damage to the zygotes. PMMA microparticles were more readily taken up than PS microparticles, which could suggest surface chemical identity as potentially modulating the affinity of larvae for specific plastics. In contrast, significantly reduced toxicity was noted for the combination of PMMA microparticles and cypermethrin (100 μg L -1 ), and may be related to less ready desorption of the pyrethroid than PS, as well as cypermethrin activating mechanisms that result in reduced feeding and hence decreased ingestion of microparticles.

Lipopolysaccharides pharmacology, Tandem Mass Spectrometry, Polymers pharmacology, Polymers chemistry, Neurons, Sulfates chemistry, and HMGB1 Protein

The objective of this study was to establish if polyglycerols with sulfate or sialic acid functional groups interact with high mobility group box 1 (HMGB1), and if so, which polyglycerol could prevent loss of morphological plasticity in excitatory neurons in the hippocampus. Considering that HMGB1 binds to heparan sulfate and that heparan sulfate has structural similarities with dendritic polyglycerol sulfates (dPGS), we performed the experiments to show if polyglycerols can mimic heparin functions by addressing the following questions: (1) do dendritic and linear polyglycerols interact with the alarmin molecule HMGB1? (2) Does dPGS interaction with HMGB1 influence the redox status of HMGB1? (3) Can dPGS prevent the loss of dendritic spines in organotypic cultures challenged with lipopolysaccharide (LPS)? LPS plays a critical role in infections with Gram-negative bacteria and is commonly used to test candidate therapeutic agents for inflammation and endotoxemia. Pathologically high LPS concentrations and other stressful stimuli cause HMGB1 release and post-translational modifications. We hypothesized that (i) electrostatic interactions of hyperbranched and linear polysulfated polyglycerols with HMGB1 will likely involve sites similar to those of heparan sulfate. (ii) dPGS can normalize HMGB1 compartmentalization in microglia exposed to LPS and prevent dendritic spine loss in the excitatory hippocampal neurons. We performed immunocytochemistry and biochemical analyses combined with confocal microscopy to determine cellular and extracellular locations of HMGB1 and morphological plasticity. Our results suggest that dPGS interacts with HMGB1 similarly to heparan sulfate. Hyperbranched dPGS and linear sulfated polymers prevent dendritic spine loss in hippocampal excitatory neurons. MS/MS analyses reveal that dPGS-HMGB1 interactions result in fully oxidized HMGB1 at critical cysteine residues (Cys23, Cys45, and Cys106). Triply oxidized HMGB1 leads to the loss of its pro-inflammatory action and could participate in dPGS-mediated spine loss prevention. LPG-Sia exposure to HMGB1 results in the oxidation of Cys23 and Cys106 but does not normalize spine density.

Humans, Micelles, Cell Line, Tumor, Polymers pharmacology, Neoplastic Stem Cells, Diflunisal pharmacology, Gallium pharmacology, Osteosarcoma drug therapy, Bone Neoplasms, and Nanoparticles

Here we report the encapsulation of an osteosarcoma stem cell (OSC) potent gallium(III)-diflunisal complex 1 into polymeric nanoparticles, and its delivery into osteosarcoma cells. At the optimum feed (20 %, 1 NP 20 ), nanoparticle encapsulation of 1 enhances potency towards bulk osteosarcoma cells and OSCs (cultured in monolayer and three-dimensional systems). Strikingly, the nanoparticle formulation exhibits up to 5645-fold greater potency towards OSCs than frontline anti-osteosarcoma drugs, doxorubicin and cisplatin. The nanoparticle formulation evokes a similar mechanism of action as the payload, which bodes well for future translation. Specifically, the nanoparticle formulation induces nuclear DNA damage, cyclooxygenase-2 downregulation, and caspase-dependent apoptosis. To the best of our knowledge, this is the first study to demonstrate that polymeric nanoparticles can be used to effectively deliver an OSC-active metal complex into osteosarcoma cells.
(© 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH.)