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1.
J Formos Med Assoc ; 121(10): 2101-2108, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35450742

RESUMO

PURPOSE: This cohort study evaluates therapeutic efficacy and adverse events (AEs) of various overactive bladder (OAB) medications for patients with central nervous system (CNS) disorders. METHODS: Patients with OAB and CNS disorders were prospectively enrolled. They were randomly allocated to 3 different treatment subgroups: (1) mirabegron 50 mg once daily (2) solifenacin 5 mg per day, and (3) combined solifenacin 5 mg and mirabegron 50 mg once daily. Efficacy and safety questionnaires and objective parameters were compared among the subgroups, and subgroups between baseline and 3 and 6 months after treatment. AEs, including cognitive dysfunction, were assessed using the Mini-Mental State Examination (MMSE). RESULTS: 102 patients (mean age, 71.8 ± 8.7 years) were enrolled, including 35, 36, and 31 patients received mirabegron monotherapy, solifenacin monotherapy, and combination therapy, respectively. OAB symptoms scores all significantly improved 3 months after treatment in different subgroup. However, PVR increased and VE decreased significantly after treatment in patients receiving solifenacin monotherapy and combination therapy. Dry mouth and constipation were the most common AEs, especially in the solifenacin and combination subgroups. Mild incidence of AEs was noted in patients receiving mirabegron monotherapy. No significant change in MMSE was noted among the subgroups after treatment. CONCLUSION: OAB medication had good therapeutic efficacy in patients who had OAB with CNS disorders, especially in cerebrovascular accident and parkinsonism. No OAB medication or their combination affected cognitive function, whereas minimal AEs were noted with mirabegron. Mirabegron could be recommended as the first choice for managing OAB in these patients.


Assuntos
Doenças do Sistema Nervoso Central , Bexiga Urinária Hiperativa , Agentes Urológicos , Acetanilidas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/tratamento farmacológico , Cognição , Estudos de Coortes , Quimioterapia Combinada/efeitos adversos , Humanos , Pessoa de Meia-Idade , Succinato de Solifenacina/efeitos adversos , Tiazóis/efeitos adversos , Resultado do Tratamento , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/efeitos adversos
2.
Langmuir ; 37(19): 5776-5782, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33966385

RESUMO

Nonspecific protein adsorption-resistant materials, the so-called nonfouling materials, are crucial biomaterials in biomedical applications. Up-to-date, little attention was paid to the biodegradability of these materials. In this work, nonfouling zwitterionic copolymerized peptides composed of the N-l-glumatyl-l-lysine dimer (EK) and δ-l-lysinyl-l-glutamic acid dimer (E-K, glutamic acid with the lysine side chain) at various ratios were synthesized to investigate the enzymatic degradation rate. Two types of proteases (trypsin and alkaline protease), which represent a site-specific and less site-specific cleavage protease, respectively, were used to demonstrate the adjustable degradability by tracking the molecular weight (Mw) at different digestion times. Results showed that higher compositions of the E-K dimer lead to slower degradation rates by both proteases and larger fragments after 120 min digestion. With the composition of the E-K dimer over 50%, the degradation of copolymerized peptides by both proteases becomes very slow. This indicated that the bulky lysinyl side chain on E-K can alter the enzymolysis process for adjusting the enzymatic degradability of the newly synthesized zwitterionic copolymerized peptides, which could be promising candidates for biomedical applications in vivo.


Assuntos
Ácido Glutâmico , Lisina , Peptídeos , Polímeros , Tripsina
3.
Langmuir ; 36(12): 3251-3259, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32154728

RESUMO

Long-term resistance of biomaterials to the bacterial biofilm formation without antibiotic or biocide is highly demanded for biomedical applications. In this work, a novel biodegradable biomaterial with excellent capability to prevent long-term bacterial biofilm formation is prepared by the following two steps. Ethylcarboxybetaine ester analogue methacrylate (ECBEMA), poly(ethylene glycol) monomethacrylate (PEGMA), and 3-methacryloxypropyletris(trimethylsiloxy)silane (TRIS) were copolymerized to obtain p(ECBEMA-PEGMA-TRIS) (PEPT). Then, PEPT was cross-linked by isocyanate-terminated polylactic acid (IPDI-PLA-IPDI) to obtain the final PEPTx-PLAy (x and y are the number-average molecular weights (Mn) of PEPT and PLA, respectively) with optimal mechanical strength and adjustable surface regeneration rate. Static contact angle measurement, protein adsorption measurement, and attenuated total reflectance infrared (ATR-IR) results show that the PEPT19800-PLA800 film surface can generate a zwitterionic layer to resist nonspecific protein adsorption after surface hydrolysis. Quartz crystal microbalance with dissipation (QCM-D) results indicates that the PEPT19800-PLA800 film can undergo gradual degradation of the surface layer at the lowest swelling rate. Particularly, this material can efficiently resist the bacterial biofilm formation of both Gram-positive bacteria and Gram-negative bacteria over 14 and 6 days, respectively. Moreover, the material also shows an ideal self-healing feature to adapt to harsh conditions. Thus, this nonfouling material shows great potential in biomedical applications and marine antifouling coatings without antibiotic or biocide.


Assuntos
Materiais Biocompatíveis , Técnicas de Microbalança de Cristal de Quartzo , Adsorção , Materiais Biocompatíveis/toxicidade , Biofilmes , Hidrólise , Propriedades de Superfície
4.
Analyst ; 144(17): 5179-5185, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31343648

RESUMO

The development of noble ultra-small biocompatible Pt nanoclusters (Pt NCs) for glucose detection has been drawing great attention. Herein, ultra-small biocompatible jujube polysaccharide (JP) stabilized platinum nanoclusters (Ptn-JP NCs) are prepared using natural JP as a reducing and solubilizing agent. Ptn-JP NCs were studied for the colorimetric detection of glucose. Ptn-JP NCs (n = 50, 200 and 400) had an average particle diameter of 1-2 nm. Particularly, the measurements of hydrodynamic sizes of Ptn-JP NCs indicated that they maintained good stability in solution for one week. Pt200-JP NCs showed good biocompatibility, and were not toxic against HeLa cells at a high concentration of 400 µg mL-1. Furthermore, Pt200-JP NCs catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with H2O2 to produce blue oxidized TMB (oxTMB). This reaction followed typical Michaelis-Menten kinetics. More importantly, the glucose concentration could be sensitively detected by the color change, and this process was not interfered by other sugars. The linear range for glucose concentration was from 0.01 to 1 mM with a detection limit of 5.47 µM. The glucose concentrations of real samples of serum using Pt200-JP NCs were 9.2, 4.9 and 6.5 mM, respectively. The prepared Ptn-JP NCs have great potential in various biomedical detection methods.


Assuntos
Glicemia/análise , Nanopartículas Metálicas/química , Polissacarídeos/química , Ziziphus/química , Benzidinas/química , Glicemia/química , Catálise , Colorimetria/métodos , Glucose Oxidase/química , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Cinética , Limite de Detecção , Nanopartículas Metálicas/toxicidade , Oxirredução , Tamanho da Partícula , Platina/química , Platina/toxicidade , Polissacarídeos/toxicidade , Saliva/química
5.
Environ Sci Technol ; 52(7): 4457-4463, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29513525

RESUMO

Zwitterions of charge-balanced units have super-low fouling properties induced by ionic solvation, but their extensive applications in polymeric substrates are strictly constrained by current constructing strategies. A zwitterion-like, charge-balanced ultrathin layer with high antifouling capacity was covalently constructed on delicate aromatic polyamide (PA) reverse osmosis (RO) membranes via a mild and solvent-free grafting-to strategy. Two oppositely charged commercial short-chain carbonyl alkenes, 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and methacryloxyethyltrimethylammonium chloride (DMC), were directly mixed-grafted with amino groups on PA RO membrane surface via Michael addition. Under ambient temperature and pressure, these oppositely charged compounds were assembled into a zwitterion-like, charge-balanced ultrathin layer. The dynamic fouling experiments indicated that the modified membrane exhibited strong antifouling properties and excellent permeation recovery abilities. Surface characterization revealed that the selective layer thickness and surface roughness were not measurably changed. More meaningful is that the typical ridge-and-valley surface structure and the excellent separation performance were both well preserved after modification. This opens a universal avenue to construct a zwitterion-like, ultrathin antifouling layer on the delicate polymer substrate without compromising its original matrix structure and performance, which has promising application in areas of biosensors, tissue engineering, and biomaterials.


Assuntos
Membranas Artificiais , Polímeros , Filtração
6.
Biomacromolecules ; 17(6): 2010-8, 2016 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-27050797

RESUMO

Blood stability, active targeting, and controlled drug release are the most important features to design desirable drug carriers. Here, we demonstrate a zwitterionic biodegradable cross-linked micelle based on a penta-block copolymer, which utilizes poly(carboxybetaine methacrylate) as hydrophilic segment, poly(ε-caprolactone) as biodegradable hydrophobic segment, poly(S-2-hydroxyethyl-O-ethyl dithiocarbonate methacrylate) (PSODMA) block as thiol protecting segment for cross-linking, and cyclic Arg-Gly-Asp-d-Tyr-Lys [c(RGDyK)] as targeting ligand. As a result, this micelle possessed excellent colloidal stability at high dilution and in 50% fetal bovine serum. In vitro drug release experiment showed no burst release under physiological conditions but accelerated drug release in mimicking tumor tissue environment. In vivo tests showed that the drug-loaded micelles had prolonged half-life in bloodstream, enhanced therapeutic efficiency, and reduced cardiac toxicity and biotoxicity compared with free drug formulation. Taken together, the reported c(RGDyK)-modified zwitterionic interfacially cross-linked micelle has emerged as an appealing platform for cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Materiais Biocompatíveis/química , Reagentes de Ligações Cruzadas/química , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Peptídeos Cíclicos/química , Polímeros/química , Animais , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Doxorrubicina/sangue , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Camundongos , Camundongos Nus , Micelas , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Langmuir ; 30(13): 3764-74, 2014 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-24617705

RESUMO

Polymer-drug conjugates are commonly used as nano drug vehicles (NDVs) to delivery anticancer drugs. Zwitterionic polymers are ideal candidates to conjugate drugs because they show higher resistance to nonspecific protein adsorption in complex media than that of nonionic water-soluble polymers, such as poly(ethylene glycol). However, the charge balance characteristics of zwitterionic polymers used as NDVs will be broken from the inclusion of additional charged groups brought by conjugated drugs or functional groups, leading to the loss of resistance to protein adsorption. Consequently, the nonspecific protein adsorption on drug carriers will cause fast clearance from the blood system, an immune response, or even severe systemic toxicity. To overcome this drawback, a model zwitterionic polymer, poly(carboxybetaine methacrylate) (pCBMA), was modified by the introduction of a negatively charged component, to neutralize the positive charge provided by the model drug, doxorubicin (DOX). A DOX-conjugated NDV which possesses excellent resistance to nonspecific protein adsorption was achieved by the formation of a strongly hydrated pCBMA shell with a slightly negative surface charge. This kind of DOX-conjugated NDV exhibited reduced cytotoxicity and prolonged circulation time, and it accelerated DOX release under mild acid conditions. In tumor-bearing mouse studies a 55% tumor-inhibition rate was achieved without causing any body weight loss. These results indicate the importance of charge tuning in zwitterionic polymer-based NDVs.


Assuntos
Antineoplásicos/farmacocinética , Betaína/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/síntese química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Adsorção , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Células COS , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/farmacocinética , Feminino , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Eletricidade Estática , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Adv Sci (Weinh) ; 11(16): e2308077, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38403462

RESUMO

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.


Assuntos
Reação a Corpo Estranho , Hidrogéis , Animais , Hidrogéis/química , Camundongos , Materiais Biocompatíveis/química , Lisina/química , Primatas , Roedores , Ácido Poliglutâmico/química
9.
Langmuir ; 29(28): 8914-21, 2013 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-23777276

RESUMO

The surface primary amines of generation five poly(amido amine) (G5 PAMAM) dendrimer were modified by different amounts of carboxybetaine acrylamide (CBAA). As a result, the fully modified molecules (CBAA-PAMAM-20, obtained from the 20:1 molar ratio of CBAA molecules to amino groups in modification solution) show excellent compatibility with protein and cells. CBAA-PAMAM-20 and fibrinogen (Fg) could coexist in solution without forming aggregation, indicating very weak interaction force between CBAA-PAMAM-20 and fibrinogen. CBAA-PAMAM-20 exhibits almost undetectable hemolytic activity, while other partially modified ones cause severe hemolysis and fibrinogen aggregation. Furthermore, the membrane of human umbilical vascular endothelial cell (HUVEC) remains intact after 24 h incubation with CBAA-PAMAM-20. The cytotoxicity assay of HUVEC cells and KB cells also showed that the CBAA-PAMAM-20 was not cytotoxic up to a 2 mg/mL concentration (>90% cell viability). In short, a thin compact layer of zwitterionic carboxybetaine could reduce the cytotoxicity of PAMAM through minimizing the interaction with protein and cell membranes, which suggest that the carboxybetaine-coated PAMAM could be a useful platform for biocompatible carriers to load contrast agents and drugs.


Assuntos
Betaína/análogos & derivados , Betaína/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Dendrímeros/química , Dendrímeros/toxicidade , Materiais Biocompatíveis/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/metabolismo , Hemólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Modelos Moleculares , Conformação Molecular , Proteínas/metabolismo , Relação Estrutura-Atividade
10.
Langmuir ; 28(4): 2137-44, 2012 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-22220597

RESUMO

The strong surface hydration layer of nonfouling materials plays a key role in their resistance to nonspecific protein adsorption. Poly(ethylene glycol) (PEG) is an effective example of materials that can resist nonspecific protein adsorption and cell adhesion. Thus, the strong interaction between water molecules and PEG was investigated through each T(2) component in water/PEG mixtures using multiexponential inversion of T(2) relaxation time measured by the Carr-Purcell-Meiboom-Gill (CPMG) sequence of low-field nuclear magnetic resonance (LF-NMR). Results show that about one water molecule is tightly bound with one ethylene glycol (EG) unit, and additional water molecules over 1:1 ratio mainly swell the PEG matrix and are not tightly bound with PEG. This result was also supported by the endothermic behavior of water/PEG mixtures measured by differential scanning calorimetry (DSC). It is believed that the method developed could be also applied to investigate various interactions between macromolecules and other small molecules without using deuterium samples, which might open a novel route to quantitatively measure guest-host interactions in the future.


Assuntos
Incrustação Biológica , Polietilenoglicóis/química , Água/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Peso Molecular , Movimento (Física)
11.
J Biomater Sci Polym Ed ; 33(8): 1012-1024, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35073220

RESUMO

Nonfouling materials have attracted increasing interest for their excellent biocompatibility and low immunogenicity. Strong hydration is believed to be the key reason for their resisting capability to nonspecific protein adsorption. However, little attention has been paid to quantifying their strong water binding capacity. In this study, we synthesized four zwitterionic polymers, including poly(sulfobetaine methacrylate) (pSBMA), poly(carboxybetaine methacrylate) (pCBMA), poly(carboxybetaine acrylamide) (pCBAA) and poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC), and compared non-freezing water of these zwitterionic polymers with typical antifouling polymer poly(ethylene glycol) (PEG) using differential scanning calorimetry (DSC). Non-freezing water of their monomers was also investigated. The non-freezing water of the polymers (per unit) is pMPC (10.7 ± 1.4) ≈ pCBAA (10.8 ± 1.5) > pCBMA (9.0 ± 0.6) > pSBMA (6.6 ± 0.4) > PEG20000 (0.60 ± 0.04). Similar trend is observed for their monomers. For all studied zwitterionic materials, they showed higher binding capacity than PEG. We attribute the stronger hydration of zwitterionic polymers to their strong electrostatic interactions.


Assuntos
Polímeros , Água , Adsorção , Varredura Diferencial de Calorimetria , Polietilenoglicóis/química , Polímeros/química , Água/química
12.
Nat Commun ; 12(1): 5327, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493717

RESUMO

Implantation-caused foreign-body response (FBR) is a commonly encountered issue and can result in failure of implants. The high L-serine content in low immunogenic silk sericin, and the high D-serine content as a neurotransmitter together inspire us to prepare poly-DL-serine (PSer) materials in mitigating the FBR. Here we report highly water soluble, biocompatible and easily accessible PSer hydrogels that cause negligible inflammatory response after subcutaneous implantation in mice for 1 week and 2 weeks. No obvious collagen capsulation is found surrounding the PSer hydrogels after 4 weeks, 3 months and 7 months post implantation. Histological analysis on inflammatory cytokines and RNA-seq assay both indicate that PSer hydrogels show low FBR, comparable to the Mock group. The anti-FBR performance of PSer hydrogels at all time points surpass the poly(ethyleneglycol) hydrogels that is widely utilized as bio-inert materials, implying the potent and wide application of PSer materials in implantable biomaterials and biomedical devices.


Assuntos
Materiais Biocompatíveis/farmacologia , Reação a Corpo Estranho/prevenção & controle , Peptídeos/farmacologia , Próteses e Implantes , Animais , Materiais Biocompatíveis/síntese química , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Citocinas/imunologia , Reação a Corpo Estranho/imunologia , Hidrogéis , Infusões Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/síntese química , Polietilenoglicóis/farmacologia , Solubilidade , Água/química
13.
ACS Appl Mater Interfaces ; 12(41): 46639-46652, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32893614

RESUMO

To augment the antitumor efficacy and minimize the significant side effects of chemotherapeutic drugs on health organs, a novel albumin-mimicking nanodrug, which is based on zwitterionic poly(glutamatyl lysine-co-cysteine) peptides scaffold, is developed to enhance pH-triggered tumor targeting via prolonging circulation time and accelerating cellular internalization. Results showed that the internalization of the nanodrug by MCF-7 cells is much faster than that by Doxil and even comparable to that by free doxorubicin (Dox) at tumor microenvironmental pH 6.7, whereas the internalization of the nanodrug is only 27.4 ± 7.6% of the Doxil by RAW-264.7 cells. Moreover, the significantly prolonged circulation time of the "stealthy" nanodrug was also comparable to that of the long circulating Doxil. As a result, the accumulation of the nanodrug in the tumor is much higher than that in the liver and kidney before the circulation half-life, which is significantly different from most other nanodrugs accumulated in the liver and kidney in this time scale. The tumor inhibition rate of the nanodrug was much higher than that of Doxil (93.2 ± 3.0% vs 54.2 ± 6.5%) after 18 day treatment, while the average bodyweight of the mice treated by the nanodrug was 26.9 ± 6.7% higher than that by Doxil. This indicated that the synergetic effect of long circulation time and fast cellular internalization of the nanodrug can significantly augment tumor targeting. This method might rejuvenate the traditional chemotherapeutic treatment.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacologia , Nanopartículas/química , Peptídeos/química , Animais , Antibióticos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Propriedades de Superfície , Fatores de Tempo , Microambiente Tumoral/efeitos dos fármacos
14.
J Mater Chem B ; 8(12): 2443-2453, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32108189

RESUMO

Although zwitterionic hydrogels exhibit excellent hemocompatibility, their extremely low tensile strength is an obstacle for their use in blood-contacting devices. Electrospun fiber scaffold-reinforced zwitterionic hydrogels are a possible solution to overcome the challenges of both mechanical strength and hemocompatibility. In this work, electrospun polyurethane (ePU) fiber scaffold-reinforced sulfobetaine methacrylate (SBMA) hydrogels (SRgels) were prepared. The SRgels exhibited 4.7 ± 0.5 MPa tensile fracture stress, while the interpenetration between the hydrogel and the fiber scaffold remained intact even under 2.8 MPa tensile stress at 3.0 mm mm-1 strain load; this confirms that the SRgels maintain excellent hemocompatibility for both blood cell adhesion and fibrinogen adsorption under physiological dynamic loading and that dynamically structural matching is achieved between the scaffold and the zwitterionic hydrogels. Mechano-induced self-enhancement was also observed after preloading more than 2.0 mm mm-1 tensile strain to resist fracture. In short, the preparation of SRgels can enable zwitterionic hydrogels to meet the requirement for mechanical strength in bio-applications as blood-contacting devices.


Assuntos
Anticoagulantes/química , Materiais Biocompatíveis/química , Hidrogéis/química , Poliuretanos/química , Adsorção , Anticoagulantes/síntese química , Anticoagulantes/farmacologia , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Hidrogéis/síntese química , Hidrogéis/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Tamanho da Partícula , Poliuretanos/síntese química , Poliuretanos/farmacologia , Propriedades de Superfície
15.
Biomaterials ; 29(32): 4285-91, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18722010

RESUMO

In this work, five self-assembled monolayers (SAMs) and three polymeric brushes with very low fibrinogen adsorption were prepared. The five SAMs are oligo(ethylene glycol) (OEG), phosphorylcholine (PC), oligo(phosphorylcholine) (OPC), and two mixed positively and negatively charged SAMs of SO(3)(-)/N(+)(CH(3))(3) (SA/TMA) and COO(-)/N(+)(CH(3))(3) (CA/TMA). Three polymer brushes were prepared on gold surfaces via surface-initiated atom transfer radical polymerization (ATRP) using three monomers, sulfobetaine methacrylate (SBMA), carboxybetaine methacrylate (CBMA), and oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Surface plasmon resonance (SPR) measurements show that although all of these surfaces are "nonfouling" to fibrinogen adsorption from buffer solution, their protein adsorption from undiluted human blood plasma varies widely. Polymer brushes exhibit much lower protein adsorption from plasma than any of the five SAMs tested. However, platelet adhesion measurements on plasma-preadsorbed surfaces show that all of these surfaces have very low platelet adhesion. Clotting time measurements using recalcified platelet poor plasma (PPP) incubation with the eight types of surfaces show that they do not shorten clotting times. Linear polymers of polySBMA and polyCBMA with similar molecular weights were also synthesized and characterized. In the presence of polyCBMA linear polymers, the clotting time of PPP was prolonged and increased with the concentration of the polymer, while no anticoagulant activity was observed for the polySBMA or PEG polymers. The unique anticoagulant activity of polyCBMA, as well as its high plasma protein adsorption resistance, makes polyCBMA a candidate for blood-contacting applications.


Assuntos
Materiais Biocompatíveis/metabolismo , Plaquetas/metabolismo , Fibrinogênio/química , Fibrinogênio/metabolismo , Adsorção , Materiais Biocompatíveis/química , Plaquetas/citologia , Soluções Tampão , Adesão Celular , Humanos , Estrutura Molecular , Polímeros/química , Soluções , Propriedades de Superfície
16.
J Phys Chem B ; 112(48): 15269-74, 2008 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-18989905

RESUMO

In this work, nonfouling zwitterionic polymers were grafted via surface-initiated atom transfer radical polymerization (ATRP) from surfaces covered with an adhesive catechol initiator. The catechol initiator was attached to both bare gold and amino-functionalized surfaces, and the nonfouling performances of the resulting polymer brushes were compared. Under optimal conditions, ultralow protein adsorption from both single-protein solutions of fibrinogen and lysozyme and complex media of 10% blood serum and 100% blood plasma/serum was achieved. Furthermore, the 3-day accumulation of Pseudomonas aeruginosa on the treated glass surfaces was studied in situ using a laminar flow chamber. The results showed that these zwitterionic coatings dramatically reduced the biofilm formation of P. aeruginosa as compared to the reference bare glass.


Assuntos
Bivalves/química , Polímeros/química , Adsorção , Animais , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biomimética , Catecóis/química , Fibrinogênio/química , Vidro , Ouro , Indicadores e Reagentes , Microscopia de Fluorescência , Muramidase/sangue , Muramidase/química , Pseudomonas aeruginosa/efeitos dos fármacos , Propriedades de Superfície
17.
Biomacromolecules ; 9(5): 1357-61, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18376858

RESUMO

This study examined six different polymer and self-assembled monolayer (SAM) surface modifications for their interactions with human serum and plasma. It was demonstrated that zwitterionic polymer surfaces are viable alternatives to more traditional surfaces based on poly(ethylene glycol) (PEG) as nonfouling surfaces. All polymer surfaces were formed using atom transfer radical polymerization (ATRP) and they showed an increased resistance to nonspecific protein adsorption compared to SAMs. This improvement is due to an increase in the surface packing density of nonfouling groups on the surface, as well as a steric repulsion from the flexible polymer brush surfaces. The zwitterionic polymer surface based on carboxybetaine methacrylate (CBMA) also incorporates functional groups for protein immobilization in the nonfouling background, making it a strong candidate for many applications such as in diagnostics and drug delivery.


Assuntos
Materiais Biocompatíveis/química , Proteínas Sanguíneas/química , Polímeros/química , Adsorção , Humanos , Íons , Plasma , Ácidos Polimetacrílicos , Soro
18.
Science ; 360(6388): 518-521, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29724951

RESUMO

The emergence of Turing structures is of fundamental importance, and designing these structures and developing their applications have practical effects in chemistry and biology. We use a facile route based on interfacial polymerization to generate Turing-type polyamide membranes for water purification. Manipulation of shapes by control of reaction conditions enabled the creation of membranes with bubble or tube structures. These membranes exhibit excellent water-salt separation performance that surpasses the upper-bound line of traditional desalination membranes. Furthermore, we show the existence of high water permeability sites in the Turing structures, where water transport through the membranes is enhanced.


Assuntos
Membranas Artificiais , Nylons , Purificação da Água/métodos , Permeabilidade , Polimerização
19.
Acta Biomater ; 71: 293-305, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29535009

RESUMO

Skin wound healing is a still long-history challenging problem and impeded by the foreign-body reaction including severe inflammation response, poor neovascularization, incomplete re-epithelialization and defective ECM remodeling. Development of biocompatible polymers, in combination with specific drugs or growth factors, has been considered as a promising strategy to treat skin wounds. Significant research efforts have been made to develop poly(ethylene glycol) PEG-based polymers for wound healing, however less efforts has been paid to zwitterionic materials, some of which have demonstrated their super low-fouling property in vitro and anti-inflammatory property in vivo. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied them to full-thickness cutaneous wounds in mice. The healing effects of SBMA hydrogels on the wound closure, re-epithelialization ratio, ECM remodeling, angiogenesis, and macrophage responses during wound healing processes were histologically evaluated by in vivo experiments. Collective results indicate that SBMA hydrogels promote full-thickness excisional acute wound regeneration in mice by enhancing angiogenesis, decreasing inflammation response, and modulating macrophage polarization. Consistently, the incorporation of SBMA into PEG hydrogels also improved the overall wound healing efficiency as compared to pure PEG hydrogels. This work demonstrates zwitterionic SBMA hydrogels as promising wound dressings for treating full-thickness excisional skin wounds. STATEMENT OF SIGNIFICANCE: Development of highly effective wound regeneration system is practically important for biomedical applications. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied it to full-thickness cutaneous wounds in mice, in comparison with PEG hydrogels as a control. We are the first to examine and reveal the difference between zwitterionic SBMA hydrogels and PEG hydrogels using a full-thickness excisional mice model. Overall, a series of in vivo systematic tests demonstrated that zwitterionic SBMA hydrogels exhibited superior wound healing property in almost all aspects as compared to PEG hydrogels.


Assuntos
Hidrogéis , Ácidos Polimetacrílicos , Reepitelização/efeitos dos fármacos , Pele Artificial , Pele , Ferimentos e Lesões , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Masculino , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Pele/irrigação sanguínea , Pele/metabolismo , Pele/patologia , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia
20.
Biomaterials ; 28(29): 4192-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17604099

RESUMO

In this work, we report a study of long-chain zwitterionic poly(sulfobetaine methacrylate) (pSBMA) surfaces grafted via atom transfer radical polymerization (ATRP) for their resistance to bacterial adhesion and biofilm formation. Previously, we demonstrated that p(SBMA) is highly resistant to nonspecific protein adsorption. Poly(oligo(ethylene glycol) methyl ether methacrylate) (pOEGMA) grafted surfaces were also studied for comparison. Furthermore, we quantify how surface grafting methods will affect the long-term biological performance of the surface coatings. Thus, self-assembled monolayers (SAMs) of alkanethiols with shorter-chain oligo(ethylene glycol) (OEG) and mixed SO3-/N+(CH3)3 terminated groups were prepared on gold surfaces. The short-term adhesion (3 h) and the long-term accumulation (24 or 48 h) of two bacterial species (Gram-positive Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa) on these surfaces were studied using a laminar flow chamber. Methyl-terminated (CH3) SAM on gold and a bare glass were chosen as references. p(SBMA) reduced short-term adhesion of S. epidermidis and P. aeruginosa relative to glass by 92% and 96%, respectively. For long-term biofilm formation, qualitative images showed that p(SBMA) dramatically reduced biofilm formation of S. epidermidis and P. aeruginosa as compared to glass.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Materiais Revestidos Biocompatíveis/farmacologia , Desinfecção/métodos , Metacrilatos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Teste de Materiais , Metacrilatos/química , Pseudomonas aeruginosa/fisiologia , Staphylococcus epidermidis/fisiologia
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