RESUMEN
Infections caused by pathogenic microorganisms have always been the Achilles heel in the clinic. In this work, to overcome this conundrum, we proposed an injectable multifunctional hydrogel material with outstanding antibacterial properties and self-healing properties and no adverse effects on health. The cross-linked hydrogel with three-dimensional (3D) networks was quickly formed via the dynamic Schiff base between amino-modified poly-tetrahydropyrimidine (PTHP-NH2) and multiple vanillin polymer P(DMA-VA) in 30 s. This hydrogel composite presents effective defense against both Gram-positive and Gram-negative bacteria, especially for the pyogenic Staphylococcus aureus. Moreover, the hydrogel showed almost no hemolysis and cytotoxicity. In vivo investigations indicated that hydrogels effectively killed S. aureus and protected against deterioration of inflammation. Besides, bioimaging of mice demonstrated that the hydrogel could be completely metabolized within 16 h. In a nutshell, given its outstanding antibacterial property and biocompatibility, the novel hydrogel could be an ideal candidate for the subcutaneous infection application.
Asunto(s)
Antibacterianos/farmacología , Infecciones por Escherichia coli/tratamiento farmacológico , Hidrogeles/farmacología , Polímeros/farmacología , Pirimidinas/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Células Cultivadas , Escherichia coli/efectos de los fármacos , Hidrogeles/síntesis química , Hidrogeles/química , Inflamación/tratamiento farmacológico , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Tamaño de la Partícula , Polímeros/síntesis química , Polímeros/química , Pirimidinas/síntesis química , Pirimidinas/química , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Skin lesions and injuries can increase the risk of pathogen infections. Developing efficacious wound dressings could effectively prevent bacterial infection and accelerate wound healing. Herein, we developed chitosan composite hydrogels cross-linked by multifunctional diazo resin (DR) as antibacterial dressings for improved wound healing. The composite hydrogels were in situ formed by electrostatic interactions, chelation interactions, and covalent bonds between carboxylated chitosan and DR under ultraviolet assisted without small photosensitizer. The resultant hydrogels (noted as DR-CCH) showed good stability at different DR concentrations in physiological buffers. The antibacterial assays showed the DR-CCH could inhibit and kill Escherichia coli and Staphylococcus aureus. What is more, our hydrogels could accelerate wound healing in vivo. The present study demonstrates this composite DR-CCH with trace zinc has potential for accelerated wound healing.
Asunto(s)
Antibacterianos/química , Vendajes , Quitosano/análogos & derivados , Hidrogeles/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Línea Celular , Quitosano/farmacología , Reactivos de Enlaces Cruzados/química , Reactivos de Enlaces Cruzados/farmacología , Compuestos de Diazonio/química , Compuestos de Diazonio/farmacología , Humanos , Hidrogeles/farmacología , Masculino , RatonesRESUMEN
Hydrogels have a wide range of applications in the fields of biomedicine, flexible electronics, and bionics. In this study, injectable and self-healable hydrogels were first prepared based on a dynamic covalent CâC bond formed via the Knoevenagel condensation reaction between poly(ethylene glycol) dicyanoacetate and water-soluble poly(vanillin acrylate). Three kinds of catalysts (phosphate buffer, zeolitic imidazolate framework-8, and tertiary amine) were used in Knoevenagel condensation for preparing hydrogels. All hydrogels in this study could be formed in situ, and their gelation time ranged from seconds to minutes. The properties and application of hydrogels could be customized according to the type of catalyst employed. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) results indicated that all the components and hydrogels exhibited low toxicity, and the hydrogels could be used as 3D cell culture scaffolds. Because of the dynamic covalent CâC bond formed by Knoevenagel condensation, the resultant hydrogels were found to be dynamic and showed good self-healing properties. This work presents a new dynamic covalent chemistry for the preparation of self-healable materials.
Asunto(s)
Hidrogeles , Polietilenglicoles , Técnicas de Cultivo de CélulaRESUMEN
A novel voriconazole (VCZ)-loaded injectable hydrogel was in situ synthetized via a Schiff base reaction between polyaldehyde dextran (PAD) and carboxymethyl chitosan (CMCTS) for intraocular drug loading and release. Water-insoluble VCZ, which is an effective agent in clinic treating fungal endophthalmitis, was loaded through the inclusion into the ß-cyclodextrin (ß-CD) cavity based on host-guest interaction on the linear poly ß-CD chain, which was in situ twined in the cross-linked hydrogel structure. The gelation time, degradation, and drug release process were investigated by studying three kinds of hydrogels with different volume ratio of PAD to CMCTS resolving in phosphate buffered saline (PBS) solution (3:7, 6:7, 9:7), respectively. The property of VCZ-loaded injectable hydrogel should be adjusted through changing the cross-linked density of the hydrogel, the molecular weight or concentration of the linear poly ß-CD to meet the treating requirement, and a multistage drug controlled-release mechanism was proposed. In conclusion, the VCZ-loaded in situ injectable hydrogel should be offered as a promising strategy for intraocular drug delivery in vitreous cavity for the treatment of fungal endophthalmitis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1909-1916, 2019.
Asunto(s)
Hidrogeles , Polisacáridos , Voriconazol , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Humanos , Hidrogeles/química , Hidrogeles/farmacocinética , Hidrogeles/farmacología , Inyecciones Intraoculares , Polisacáridos/química , Polisacáridos/farmacocinética , Polisacáridos/farmacología , Bases de Schiff/química , Bases de Schiff/farmacocinética , Bases de Schiff/farmacología , Voriconazol/química , Voriconazol/farmacocinética , Voriconazol/farmacologíaRESUMEN
The Michael addition and alkylation reaction of active methylene compounds (AMCs) with two active hydrogens had been investigated extensively in organic chemistry, while the polymerization of AMCs had few studies. Herein, we reported active methylene-based polyaddition and polyalkylation catalyzed via an organic superbase under ambient conditions. A model polymerization was first conducted between ethylene glycol diacrylate (EGDA) and methyl cyanoacetate (MCA). The molecular weight (M w) of the model polymer was up to 50 500 g mol-1 with a high yield (99%). Eight AMCs were selected and a high-throughput parallel synthesizing instrument (HTPSI) was used to synthesize semi-library polymers of AMCs and EGDA via a Michael type polyaddition. The obtained AMC-based polymers had low cell cytotoxicity. Elastomers with cyanogen groups could be prepared using trimethylolpropane triacrylate (TMPTA) as a crosslinker. Furthermore, three dihalogen compounds were explored to polymerize with MCA and malononitrile via alkylation reactions. The pendent cyanogen or ester groups of the polymers could be reduced by lithium aluminum hydride. Novel polymer families were constructed based on the polyaddition and polyalkylation of AMCs.
RESUMEN
Conventional drugs used for cancer chemotherapy have severe toxic side effects and show individually varied therapeutic responses. The convergence of nanotechnology, biology, material science and pharmacy offers a perspective strategy for cancer chemotherapy. Nanoparticles loaded with anti-cancer drug have been designed to overcome the limitations associated with conventional drugs, several nanomedicines have been approved by FDA and shown good performances in clinical practice. However, the therapeutic efficacies cannot be enhanced. Taking this into account, stimuli responsive nanoparticles present the ability to enhance therapeutic efficacy and reduce side effects. In this review, we systematically summarized the recent progresses of controlled anti-cancer drug release systems based on nanoparticles with different stimuli response including pH, temperature, light, redox and others. If the achievements of the past can be extrapolated into the future, it is highly likely that responsive nanoparticles with a wide array of desirable properties can be eventually developed for safe and efficient cancer therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Disponibilidad Biológica , Preparaciones de Acción Retardada/uso terapéutico , Portadores de Fármacos/uso terapéutico , Liberación de Fármacos , Humanos , Nanopartículas/uso terapéutico , Oxidación-Reducción , Tamaño de la Partícula , Permeabilidad , Propiedades de SuperficieRESUMEN
Microporous, hollow, or macroporous polymer spheres were prepared by a seed emulsion polymerisation method. Different from the conventional seeded emulsion polymerization, the sorbitan monooleate (Span 80) was added to the seeded emulsion polymerization. In this study, the monodisperse PS seeds prepared by dispersion polymerization were swelled by dibutyl phthalate (DBP), glycidyl methacrylate (GMA), divinylbenzene (DVB) and Span 80 successively. The effect of the amount of Span 80 on the morphology of microspheres was investigated. As different amount of Span 80 was added to the mixture, the poly(glycidyl methacrylate-divinylbenzene) (PGMA-DVB) microspheres showed a variety of morphologies containing microporous, hollow, and macroporous structure. In addition, uniform hollow particles with different pore size can be obtained through adjusting the amount of Span 80.
RESUMEN
A redox-responsive amphiphilic polymeric prodrug was synthesized in a facile way by polycondensation of oligo(ethylene glycol) with dicarboxylic acids including malic acid and 3,3'-dithiodipropionic acid , followed by esterification with ibuprofen, which was used as a model drug. Because of its amphiphilic nature and relatively high molecular weight, this polymeric prodrug can form stable micelles in aqueous media with a low critical micellar concentration (CMC). Free ibuprofen molecules can be steadily incorporated into the core of these micelles with a surprisingly high loading content (38.9 wt%), owing to hydrophobic interaction and π-π stacking with the ibuprofen moieties in the copolymer. The in vitro release results indicate that there was a relatively slow and sustained release of the conjugated ibuprofen moieties, while encapsulated ibuprofen molecules showed a rapid release. Furthermore, for both the conjugated ibuprofen and the encapsulated ibuprofen there was an accelerated release in the presence of 10 mM dl-dithiothreitol due to cleavage of the disulfide bonds, which lead to disassociation of the micelles. Notably, this prodrug was revealed to have excellent cell compatibilities via a cell counting kit-8 (CCK-8) assay. Confocal laser scanning microscope observations indicated that the micelles based on the polymeric prodrug can be taken up quickly by cells and present a redox-responsive drug release in cytoplasm. This kind of polymeric nanocarrier with a high drug loading content, low CMC, excellent biocompatibility and rapid response to a reductive environment may have tremendous scope in the area of controlled drug delivery.