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1.
J Med Microbiol ; 69(6): 874-880, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32459619

RESUMO

Introduction. Biological adhesives and effective topical therapeutic agents that improve wound healing are urgently required for the treatment of chronic ulcers. A biodegradable adhesive based on a carbohydrate polymer with zinc oxide (CPZO) was shown to possess anti-inflammatory activity and enhance wound healing, but its bactericidal activity was unknown.Aim. To investigate the bactericidal activity of CPZO against bacteria commonly present as infectious agents in chronic wounds.Methodology. We examined the bactericidal activity of CPZO against three biofilm-producing bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) through three strategies: bacterial suspension, biofilm disruption and in vitro wound biofilm model.Results. In suspension cultures, CPZO had direct, potent bactericidal action against S. aureus within 24 h, whereas E. coli took 7 days to be eliminated. By contrast, P. aeruginosa survived up to 14 days with CPZO. CPZO had biofilm disruption activity against clinical isolates of S. aureus in the anti-biofilm test. Finally, in the in vitro wound biofilm model, CPZO dramatically reduced the bacterial viability of S. aureus and P. aeruginosa.Conclusions. Together with its previously shown anti-inflammatory properties, the bactericidal activity of CPZO gives it the potential to be a first-line therapeutic option for chronic various ulcers and, possibly, other chronic ulcers, preventing or controlling microbial infections, and leading to the healing of such complicated chronic ulcers.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Carboidratos/farmacologia , Polímeros/farmacologia , Cicatrização/efeitos dos fármacos , Óxido de Zinco/farmacologia , Infecções Bacterianas/microbiologia , Biofilmes/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos
2.
AAPS PharmSciTech ; 21(4): 121, 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32337630

RESUMO

Multidrug resistance is the major problem in cancer treatment nowadays. Compounds from plants are the new targets to solve this problem. Quercetin (QCT), quercetrin (QTR), and rutin (RUT) are potential anticancer flavonoids but their poor water solubility leads to less efficacy. In this study, the polymeric micelles of benzoylated methoxy-poly (ethylene glycol)-b-oligo(ε-caprolactone) or mPEG-b-OCL-Bz loading with the flavonoids were prepared to solve these problems. The flavonoid-loaded micelles showed an average size of 13-20 nm and maximum loading capacity of 35% (w/w). The release of QCT (21%, 3 h) was lower than that of QTR (51%, 3 h) and RUT (58%, 3 h). QCT (free and micelle forms) exhibited significantly higher cytotoxicity against P-glycoprotein-overexpressing leukemia (K562/ADR) cells than QTR and RUT (p < 0.05). The results demonstrated that QCT-loaded micelles effectively reversed cytotoxicity of both doxorubicin (multidrug resistant reversing (δ) values up to 0.71) and daunorubicin (δ values up to 0.74) on K562/ADR cells. It was found that QCT-loaded micelles as well as empty polymeric micelles inhibited P-gp efflux of tetrahydropyranyl Adriamycin. Besides, mitochondrial membrane potential was decreased by QCT (in its free form and micellar formation). Our results suggested that the combination effects of polymeric micelles (inhibiting P-gp efflux) and QCT (interfering mitochondrial membrane potential) might be critical factors contributing to the reversing multidrug resistance of K562/ADR cells by QCT-loaded micelles. We concluded that QCT-loaded mPEG-b-OCL-Bz micelles are the attractive systems for overcoming multidrug-resistant cancer cells.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/síntese química , Antineoplásicos/síntese química , Flavonoides/síntese química , Micelas , Polietilenoglicóis/síntese química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Humanos , Células K562 , Polietilenoglicóis/farmacologia , Polímeros/síntese química , Polímeros/farmacologia , Solubilidade
3.
J Biosci Bioeng ; 130(2): 212-216, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32312490

RESUMO

To clinically apply bioartificial livers (BALs), an effective liver cell cryopreservation method is required for a stable cell supply. In this study, we performed tissue-engineered construct (TEC) cryopreservation of fetal liver cells (FLCs) in which FLCs cultured within a porous polymer scaffold were cryopreserved. Growth and albumin secretion in TEC-cryopreserved FLCs after thawing were compared to freshly isolated FLCs (control experiments). The effect of preculture duration prior to cryopreservation (0-3 weeks) on these functions was also examined. In the three-dimensional cultures, the TEC-cryopreserved FLCs with preculturing showed constant growth, and this growth was comparable to controls. On the contrary, the TEC-cryopreserved FLCs without preculturing did not proliferate after thawing. Albumin secretion of TEC-cryopreserved FLCs with preculturing rapidly increased up to day 12 and high secretory activity comparable to controls was maintained thereafter in FLCs with 1- or 2-week preculturing, suggesting this as an appropriate preculture duration. Compared to conventionally cryopreserved FLCs, growth and albumin secretion in the TEC-cryopreserved FLCs were significantly higher, indicating their usefulness as a potent cell source for BALs.


Assuntos
Albuminas/metabolismo , Hepatócitos/citologia , Fígado Artificial , Polímeros/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Sobrevivência Celular , Células Cultivadas , Criopreservação/normas , Feto , Fígado/citologia , Camundongos , Polímeros/farmacologia , Porosidade
4.
Expert Rev Med Devices ; 17(5): 443-460, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32176853

RESUMO

Introduction: Traditional mechanical closure techniques pose many challenges including the risk of infection, tissue reaction, and injury to both patients and clinicians. There is an urgent need to develop tissue adhesive agents to reform closure technique. This review examined a variety of tissue adhesive agents available in the market in an attempt to gain a better understanding of intracorporal tissue adhesive agents as medical devices.Areas covered: Fundamental principles and clinical determinants of the tissue adhesives were summarized. The available tissue adhesives for intracorporal use and their relevant clinical evidence were then presented. Lastly, the perspective of future development for intracorporal tissue adhesive were discussed. Clinical evidence shows current agents are efficacious as adjunctive measures to mechanical closure and these agents have been trialed outside of clinical indications with varied results.Expert opinion: Despite some advancements in the development of tissue adhesives, there is still a demand to develop novel technologies in order to address unmet clinical needs, including low tensile strength in wet conditions, non-controllable polimerization and sub-optimal biocompatibility. Research trends focus on producing novel adhesive agents to remit these challenges. Examples include the development of biomimetic adhesives, externally activated adhesives, and multiple crosslinking strategies. Economic feasibility and biosafety are limiting factors for clinical implementation.


Assuntos
Adesivos Teciduais/farmacologia , Animais , Materiais Biocompatíveis/economia , Materiais Biocompatíveis/farmacologia , Humanos , Polímeros/farmacologia , Eletricidade Estática , Adesivos Teciduais/economia
5.
Soft Matter ; 16(11): 2725-2735, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32115597

RESUMO

Transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) (PI-b-PEG) polymersomes were investigated for their potential use in the detoxification of ammonia, a metabolite that is excessively present in patients suffering from urea cycle disorders and advanced liver diseases, and which causes neurotoxic effects (e.g., hepatic encephalopathy). Polymers varying in PI and PEG block length were synthesized via nitroxide-mediated polymerization and screened for their ability to self-assemble into polymersomes in aqueous media. Ammonia sequestration by the polymersomes was investigated in vitro. While most vesicular systems were able to capture ammonia in simulated intestinal fluids, uptake was lost in partially dehydrated medium mimicking conditions in the colon. Polymeric crosslinking of residual olefinic bonds in the PI block increased polymersome stability, partially preserving the ammonia capture capacity in the simulated colon environment. These more stable vesicular systems hold promise for the chronic oral treatment of hyperammonemia.


Assuntos
Amônia/química , Portadores de Fármacos/química , Encefalopatia Hepática/tratamento farmacológico , Inativação Metabólica/genética , Amônia/metabolismo , Butadienos/química , Butadienos/farmacologia , Portadores de Fármacos/farmacologia , Fluoresceína-5-Isotiocianato/química , Hemiterpenos/química , Hemiterpenos/farmacologia , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Hepatopatias/complicações , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Metacrilatos/química , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polimerização , Polímeros/química , Polímeros/farmacologia , Força Próton-Motriz/efeitos dos fármacos , Distúrbios Congênitos do Ciclo da Ureia/complicações , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológico , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Água/metabolismo
6.
Sci Adv ; 6(4): eaax8258, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32042897

RESUMO

Patch plays an important role in clinical medicine for its broad applications in tissue repair and regeneration. Here, inspired by the diverse adhesion, anti-adhesion, and responsive structural color phenomena in biological interfaces, we present a hybrid hydrogel film with an adhesive polydopamine (PDA) layer and an anti-adhesive poly(ethylene glycol) diacrylate (PEGDA) layer in an inverse opal scaffold. It was demonstrated that the resultant hydrogel film could serve as a functional tissue patch with an excellent adhesion property on one surface for repairing injured tissues and an anti-adhesion property on the other surface for preventing adverse adhesion. Besides, because of the responsive structural color, the patch was imparted with self-reporting mechanical capability, which could provide a real-time color-sensing feedback to monitor the heartbeat activity. Moreover, the catechol groups on PDA imparted the patch with high tissue adhesiveness and self-healing capability in vivo. These features give the bioinspired patch high potential in biomedical applications.


Assuntos
Hidrogéis , Indóis , Membranas Artificiais , Polietilenoglicóis , Polímeros , Adesivos Teciduais , Animais , Anisotropia , Hidrogéis/química , Hidrogéis/farmacologia , Indóis/química , Indóis/farmacologia , Camundongos , Células NIH 3T3 , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia
7.
Nat Commun ; 11(1): 357, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953423

RESUMO

Hypoxia of solid tumor compromises the therapeutic outcome of photodynamic therapy (PDT) that relies on localized O2 molecules to produce highly cytotoxic singlet oxygen (1O2) species. Herein, we present a safe and versatile self-assembled PDT nanoagent, i.e., OxgeMCC-r single-atom enzyme (SAE), consisting of single-atom ruthenium as the active catalytic site anchored in a metal-organic framework Mn3[Co(CN)6]2 with encapsulated chlorin e6 (Ce6), which serves as a catalase-like nanozyme for oxygen generation. Coordination-driven self-assembly of organic linkers and metal ions in the presence of a biocompatible polymer generates a nanoscale network that adaptively encapsulates Ce6. The resulted OxgeMCC-r SAE possesses well-defined morphology, uniform size distribution and high loading capacity. When conducting the in situ O2 generation through the reaction between endogenous H2O2 and single-atom Ru species of OxgeMCC-r SAE, the hypoxia in tumor microenvironment is relieved. Our study demonstrates a promising self-assembled nanozyme with highly efficient single-atom catalytic sites for cancer treatment.


Assuntos
Nanopartículas/química , Fotoquimioterapia/métodos , Porfirinas/química , Oxigênio Singlete/química , Oxigênio Singlete/farmacologia , Animais , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis , Catalase/química , Catalase/uso terapêutico , Linhagem Celular Tumoral , Células HEK293 , Células HeLa , Humanos , Peróxido de Hidrogênio/farmacologia , Camundongos , Nanopartículas/uso terapêutico , Nanotecnologia , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Polímeros/farmacologia , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
8.
Chem Commun (Camb) ; 56(16): 2415-2418, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31994584
9.
Chem Commun (Camb) ; 56(16): 2459-2462, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31996889

RESUMO

A thermoresponsive NIPAAm-based polymer is combined with the selective acetylcholinesterase inhibitor tacrine in order to create a strict in sense on/off switch for enzymatic activity. This polymer-inhibitor conjugate inhibits AChE at room temperature and enables reactivation of AChE by heating above the cloud point of the conjugate.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Polímeros/farmacologia , Tacrina/farmacologia , Temperatura , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Estrutura Molecular , Polímeros/síntese química , Polímeros/química , Tacrina/síntese química , Tacrina/química
10.
Carbohydr Polym ; 231: 115687, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888837

RESUMO

The intractable toxicity of cationic polymers limits their applicability in gene transport and controlled release. In consideration of the good biocompatibility and biofunctionality of dextran, herein we design and synthesize two types of amino group-containing cationic copolymers based on dextran by the copolymerization of cationic monomers from dextran backbones. Additionally, allyl crosslinkers containing disulfide bonds were introduced into polymerization, that made the copolymer crosslinked by disulfide. The resultant coacervates were formed from the self-assembly of cationic coplymers and anionic genes, and redox-responsive disulfide branch points endow coacervates with reducing environment responsiveness. The in vitro experiments showed that the dextran-based coacervates were sensitive to the reducing environment and underwent cleavage, which resulted in an effective release, uptake, and transfection of the genes by 293T cells. In addition, dextran-based coacervates can be used to carry siRNA into cancer cells with a high transfection efficiency, demonstrating their potential applicability in treatment against cancer.


Assuntos
Técnicas de Transferência de Genes , Neoplasias/genética , Polímeros/química , RNA Interferente Pequeno/genética , Ânions/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cátions/química , Proliferação de Células/genética , Dextranos/química , Dissulfetos/química , Células HEK293 , Humanos , Neoplasias/terapia , Oxirredução , Polímeros/farmacologia , RNA Interferente Pequeno/farmacologia , Transfecção
11.
Appl Microbiol Biotechnol ; 104(5): 1823-1835, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31925482

RESUMO

The current demand for new antimicrobial systems has stimulated research for the development of poly(lactic acid)/carvacrol (PLA/CAR)-based materials able to hinder the growth and spread of microorganisms. The eco-friendly characteristics of PLA and cytocompatibility make it very promising in the perspective of green chemistry applications as material for food and biomedical employments. The broad-spectrum biological and pharmacological properties of CAR, including antimicrobial activity, make it an interesting bioactive molecule that can be easily compounded with PLA by adopting the same techniques as those commonly used for PLA manufacturing. This review critically discusses the most common methods to incorporate CAR into a PLA matrix and their interference on the morphomechanical properties, release behavior, and antimicrobial activity of systems. The high potential of PLA/CAR materials in terms of chemical-physical and antimicrobial properties can be exploited for the future development of food packaging, coated medical devices, or drug delivery systems.


Assuntos
Antibacterianos/química , Cimenos/química , Poliésteres/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Cimenos/farmacologia , Embalagem de Alimentos/instrumentação , Poliésteres/farmacologia , Polímeros/síntese química , Polímeros/farmacologia
12.
Nanoscale ; 12(3): 1801-1810, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31898712

RESUMO

Black titanium dioxide (TiO2) nanoparticles have attracted great attention due to their application in photothermal therapy (PTT). However, single-mode phototherapy has the risk of recurrence, and the high-dose laser usually imposed to improve the PTT performance can bring a potential threat to security. Here, polydopamine (PDA)-coated black TiO2 (b-P25@PDA) nanoparticles with a core-shell structure were synthesized for enhanced PTT; then, synergistic phototherapy nanoprobes (b-P25@PDA-Ce6 (Mn)) were constructed by coupling chlorin e6 (Ce6) and chelating Mn2+ for simultaneous photodynamic therapy (PDT)/PTT and magnetic resonance (MR) imaging, in which a low-dose laser was used and imaging-guided phototherapy with high efficiency and high safety was achieved. The prepared nanoprobes showed high photothermal conversion efficiency (32.12%), high reactive oxygen generation and excellent MR imaging. In the 4T1 tumor-bearing nude mouse model, the tumors completely disappeared under the combination of PDT/PTT with a low-dose laser but were only partially inhibited by single PDT and single PTT. The current work developed a multifunctional black TiO2-based nanoprobe for enhanced synergistic PDT/PTT and MR imaging, which will be important for the safe and efficient visualized theranostics of cancers.


Assuntos
Meios de Contraste , Indóis , Imagem por Ressonância Magnética , Neoplasias Mamárias Animais , Manganês , Nanopartículas , Fototerapia , Polímeros , Porfirinas , Titânio , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacologia , Feminino , Indóis/química , Indóis/farmacologia , Neoplasias Mamárias Animais/diagnóstico por imagem , Neoplasias Mamárias Animais/tratamento farmacológico , Manganês/química , Manganês/farmacologia , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Polímeros/química , Polímeros/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Titânio/química , Titânio/farmacologia
13.
Eur J Med Chem ; 187: 111924, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855792

RESUMO

Cancer and malaria remain relevant pathologies in modern medicinal chemistry endeavours. This is compounded by the threat of development of resistance to existing clinical drugs in use as first-line option for treatment of these diseases. To counter this threat, strategies such as drug repurposing and hybridization are constantly adapted in contemporary drug discovery for the expansion of the drug arsenal and generation of novel chemotypes with potential to avert or delay resistance. In the present study, a polymer precursor scaffold, 1,3-benzoxazine, has been repurposed by incorporation of an organometallic ferrocene unit to produce a novel class of compounds showing in vitro biological activity against breast cancer, malaria and trypanosomiasis. The resultant ferrocenyl 1,3-benzoxazine compounds displayed high potency and selectivity against the investigated diseases, with IC50 values in the low and sub-micromolar range against both chloroquine-sensitive (3D7) and resistant (Dd2) strains of the Plasmodium falciparum parasite. On the other hand, antitrypanosomal (Trypanosoma brucei brucei) potencies were observed between 0.15 and 38.6 µM. The majority of the compounds were not active against breast cancer cells (HCC70), however, for the toxic compounds, IC50 values ranged from 11.0 to 30.5 µM. Preliminary structure-activity relationships revealed the basic oxazine sub-ring and lipophilic benzene substituents to be conducive for biological efficacy of the ferrocenyl 1,3-benzoxazines reported in the study. DNA interaction studies performed on the most promising compound 4c suggested that DNA damage may be one possible mode of action of this class of compounds.


Assuntos
Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Benzoxazinas/farmacologia , Reposicionamento de Medicamentos , Plasmodium falciparum/efeitos dos fármacos , Polímeros/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Antimaláricos/síntese química , Antimaláricos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Benzoxazinas/síntese química , Benzoxazinas/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Dinâmica Molecular , Estrutura Molecular , Testes de Sensibilidade Parasitária , Polímeros/síntese química , Polímeros/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
14.
Ultrasonics ; 101: 106033, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31561207

RESUMO

The objective of this study was to use ultrasound in combination with nanoparticulate formulations of taxane drugs for an additive approach to overcome multidrug resistance (MDR). Polymeric nanoparticulate formulations containing both chemotherapeutic taxane drugs and a polymeric inhibitor (MePEG17-b-PCL5) of drug resistant proteins have been previously developed in an attempt to overcome MDR in cells. High frequency (>1 MHz) ultrasound has been shown to increase the uptake of cytotoxic drugs in MDR proliferating cells and has been suggested as a different way to overcome MDR, resensitize drug resistant cancer cells and allow for chemotherapeutic efficacy. MDCK-MDR cells were incubated with docetaxel (DTX) or paclitaxel (PTX) loaded, solid core, nanoparticles made from a 50:50 ratio of two diblock copolymers, MePEG114-b-PCL200 and MePEG17-b-PCL5 (PCL200/PCL5). The accumulation of drug in MDCK-MDR cells was measured using radiolabeled drug and the viability of cells was determined using an MTS cell proliferation assay. The effect of ultrasound (4 MHz, 32 W/cm2, 10 s, 25% duty cycle) on drug uptake and cell viability was studied. Using free DTX or PTX, MDCK-MDR cells were killed at sublethal doses of drug with the P-gp inhibitor (MePEG17-b-PCL5) present at a concentration of just 0.006% (m/v) and cell death began after just 3 h of incubation. Using sublethal incubation doses of PTX or DTX in PCL200/PCL5 nanoparticles for 90 min, followed by a second exposure to blank PCL200/PCL5 nanoparticles, cell viability dropped by approximately 60% at 24 h. Drug accumulation increased by 1.43-1.9 fold following five bursts of ultrasound applied at 90 min. Both, increased ultrasound exposure and increased concentrations of blank nanoparticles during the second incubation allowed for increased levels of cell death. The combined use of ultrasound with taxane and P-gp inhibitor loaded polymeric nanoparticles may allow for increased accumulation of drug and inhibitor which may then release both agents inside cells in a controlled manner to overcome drug resistance in MDR cells.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos Fitogênicos/farmacologia , Docetaxel/farmacologia , Nanopartículas/química , Paclitaxel/farmacologia , Polietilenoglicóis/farmacologia , Ondas Ultrassônicas , Animais , Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Docetaxel/química , Cães , Sistemas de Liberação de Medicamentos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Paclitaxel/química , Polietilenoglicóis/química , Polímeros/química , Polímeros/farmacologia , Células Tumorais Cultivadas
15.
Mater Sci Eng C Mater Biol Appl ; 107: 110225, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761201

RESUMO

Role of sulfur (S) and nitrogen (N) groups in promoting cell adhesion or commonly known as biocompatibility, is well established, but their role in reducing bacterial attachment and growth is less explored or not well-understood. Natural sulfur-based compounds, i.e. sulfide, sulfoxide and sulfinic groups, have shown to inhibit bacterial adhesion and biofilm formation. Hence, we mimicked these surfaces by plasma polymerizing thiophene (ppT) and air-plasma treating this ppT to achieve coatings with S of similar oxidation states as natural compounds (ppT-air). In addition, the effects of these N and S groups from ppT-air were also compared with the biocompatible amine-amide from n-heptylamine plasma polymer. Crystal violet assay and live and dead fluorescence staining of E. coli and S. aureus showed that all the N and S coated surfaces generated, including ppHA, ppT and ppT-air, produced similarly potent, growth reduction of both bacteria by approximately 65% at 72 h compared to untreated glass control. The ability of osteogenic differentiation in Wharton's jelly mesenchymal stem cells (WJ-MSCs) were also used to test the cell biocompatibility of these surfaces. Alkaline phosphatase assay and scanning electron microscopy imaging of these WJ-MSCs growths indicated that ppHA, and ppT-air were cell-friendly surfaces, with ppHA showing the highest osteogenic activity. In summary, the N and S containing surfaces could reduce bacteria growth while promoting mammalian cell growth, thus serve as potential candidate surfaces to be explored further for biomaterial applications.


Assuntos
Materiais Biocompatíveis/química , Nitrogênio/química , Polímeros/química , Enxofre/química , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Gases em Plasma/química , Polímeros/farmacologia , Propriedades de Superfície , Geleia de Wharton/citologia
16.
Mater Sci Eng C Mater Biol Appl ; 106: 110293, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753347

RESUMO

The inadequate donor source and the difficulty of using natural grafts in tendon repair and regeneration has led researchers to develop biodegradable and biocompatible synthetic based tissue equivalents. Poly(glycerol sebacate) (PGS) is a surface-erodible bioelastomer and has been increasingly investigated in a variety of biomedical applications. In this study, PGS elastomeric sheets were prepared by using a facile microwave method and used as elastomeric platform for the first time under mechanical stimulation to induct the tenocyte gene expression. It is revealed that elastomeric PGS sheets promote progenitor tendon cell structure by increasing proliferation and gene expression with regard to tendon extracellular matrix components. Human tenocytes were seeded onto poly(glycerol-sebacate) sheets and were cultured two days prior to transfer to dynamic culture in a bioreactor system. Cell culture studies were carried out for 12 days under 0%, 3% and 6% strain at 0.33 Hz. The PGS-cell constructs were examined by using Scanning Electron Microscopy (SEM), cell viability via live/dead staining using confocal microscopy, and GAG/DNA analysis. In addition, gene expression was examined using real-time polymerase chain reaction (RT-PCR). Tenocytes cultured upon PGS scaffolds under 6% cyclic strain exhibited tendon-like gene expression profile compared to 3% and 0% strain groups. The results of this study show that PGS is a suitable material in promoting tendon tissue formation under dynamic conditions.


Assuntos
Decanoatos/química , Glicerol/análogos & derivados , Polímeros/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Reatores Biológicos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Decanoatos/farmacologia , Glicerol/química , Glicerol/farmacologia , Humanos , Polímeros/farmacologia , Tenócitos/citologia , Tenócitos/metabolismo , Tecidos Suporte/química , Transcriptoma/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
17.
Mater Sci Eng C Mater Biol Appl ; 107: 110325, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761222

RESUMO

Synthesis of nanomaterials having uniform shape and size is a challenging task. Properties exhibited by such substrates would be compatible and homogeneous compared to the average properties displayed by those substrates with heterogeneous size. Herein, we report the synthesis of polypyrrole nanorods (PPy-NRs) of almost uniform size via oxidative chemical polymerization of pyrrole within anodized aluminum oxide nanopores followed by sacrificial removal of the template. Field emission scanning electron microscopy (FE-SEM), fourier transformed infra-red (FT-IR) spectra, X-ray diffraction (XRD), and ultra-violet-visible-near infra-red (UV-Vis-NIR) spectra of the substrate were used to analyze the physicochemical properties of as-synthesized PPy-NRs. PPy-NRs treated MC3T3-E1 and PC12 cells exhibited good biocompatibility in CCK-8 and live/dead assays. The assay showed more cell viability on PC12 cell lines. Electrical stimulation through PPy-NRs treated PC12 cells accelerated neuronal differentiation compared to those without electrical stimulation during in vitro cell culture.


Assuntos
Nanoporos , Nanotubos/química , Neurônios/efeitos dos fármacos , Polímeros/síntese química , Polímeros/farmacologia , Pirróis/síntese química , Pirróis/farmacologia , Óxido de Alumínio/isolamento & purificação , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular , Estimulação Elétrica , Camundongos , Microscopia Eletrônica de Varredura , Neurônios/fisiologia , Osteoblastos/efeitos dos fármacos , Células PC12 , Polimerização , Ratos , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
18.
Colloids Surf B Biointerfaces ; 185: 110605, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31722285

RESUMO

Polymeric coatings with positive surface charge offer potential antimicrobial activity, which they owe to a simple electrostatic attraction with negatively charged bacterial walls and membranes. We describe synthesis and characterization of poly(2-aminoethyl methacrylate) and its copolymers with methyl methacrylate and butyl acrylate, as potential binders for antimicrobial solvent-cast paints. TiO2 and CaCO3 mineral particles were employed as model pigments/fillers, as they are used in most real-life paint formulations. Electrokinetic (ζ) potential and antimicrobial activity of thin films made of the (co)polymers in the absence and presence of TiO2 and CaCO3 nanopowders were assessed using streaming current measurements and microbial growth inhibition tests, respectively. Independently of the structure of the monomers used for the synthesis, the films showed positive ζ-potential values (up to +95 mV) in the pH range 3.5-8.0. The presence of mineral particles at 50% dry weight of the films did not affect significantly the ζ(pH) curves. The films made of the mixed dispersions remained positively charged and inhibited growth of both Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, as well as yeast (C. albicans). The mixed polymeric-mineral films described in this study seem to be promising potential candidates for designing antimicrobial coatings aimed to prevent spreading of bacterial infections.


Assuntos
Anti-Infecciosos/farmacologia , Carbonato de Cálcio/farmacologia , Metacrilatos/farmacologia , Polímeros/farmacologia , Titânio/farmacologia , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Carbonato de Cálcio/química , Fungos/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Metacrilatos/síntese química , Metacrilatos/química , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Polímeros/síntese química , Polímeros/química , Espectroscopia de Prótons por Ressonância Magnética , Titânio/química
19.
Toxicol Appl Pharmacol ; 386: 114833, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756429

RESUMO

One of the main problems for the development of pulmonary formulations is the low availability of approved excipients. Polyglycerol esters of fatty acids (PGFA) are promising molecules for acting as excipient for formulation development and drug delivery to the lung. However, their biocompatibility in the deep lung has not been studied so far. Main exposed cells include alveolar epithelial cells and alveolar macrophages. Due to the poor water-solubility of PGFAs, the exposure of alveolar macrophages is expected to be much higher than that of epithelial cells. In this study, two PGFAs and their mixture were tested regarding cytotoxicity to epithelial cells and cytotoxicity and functional impairment of macrophages. Cytotoxicity was assessed by dehydrogenase activity and lactate dehydrogenase release. Lysosome function, phospholipid accumulation, phagocytosis, nitric oxide production, and cytokine release were used to evaluate macrophage function. Cytotoxicity was increased with the increased polarity of PGFA molecules. At concentrations above 1 mg/ml accumulation in lysosomes, impairment of phagocytosis, secretion of nitric oxide, and increased release of cytokines were noted. The investigated PGFAs in concentrations up to 1 mg/ml can be considered as uncritical and are promising for advanced pulmonary delivery of high powder doses and drug targeting to alveolar macrophages.


Assuntos
Excipientes/farmacologia , Excipientes/toxicidade , Ácidos Graxos/toxicidade , Glicerol/toxicidade , Polímeros/toxicidade , Células A549 , Administração por Inalação , Proteínas Aviárias/metabolismo , Citocinas/metabolismo , Excipientes/administração & dosagem , Ácidos Graxos/administração & dosagem , Ácidos Graxos/farmacologia , Glicerol/administração & dosagem , Glicerol/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Fagocitose/efeitos dos fármacos , Polímeros/administração & dosagem , Polímeros/farmacologia , Alvéolos Pulmonares/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Testes de Toxicidade
20.
ACS Appl Mater Interfaces ; 12(1): 1588-1596, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31840506

RESUMO

Antifouling surfaces with optimized conformation and compositional heterogeneities are presented with the goal of improving the efficacy of surface protection. The approach exploits the adhesive group (thiol or catechol chain end) to anchor asymmetric polymer brushes (APBs) bearing amphiphilic side chains with synergistic nonfouling and fouling-release abilities onto the surface. The conformation of the APB surface is close to the fencelike structure, which mimics lubricating protein lubricin, endowing the surface with capacity of enhanced protection and antiadhesivity, even facing the high compression of fouling. By utilizing a poly(Br-acrylate-alkyne) macroagent comprising alkynyl and 2-bromopropionate groups, we prepared a series of APB surfaces based on polyacrylate-g-poly(ethylene oxide)/poly(pentafluorophenyl methacrylate) (PA-g-PEO/PPFMA) APBs to explore the influence of the content of the fluorinated segment and bioinspired topological polymer chemistry on their antifouling performance. The APB surfaces can not only provide compositional heterogeneities of PEO and fluorinated segments in each side chain but also give a high surface coverage because of the characteristic of high grafting density of macromolecular brushes. It was found for the first time, as far as we are aware, the fencelike APB surface shows excellent antifouling performance with less protein adsorption (up to 91% off) and cell adhesion (up to 84% off) in comparison with the controlled substrate under relatively long incubation time.


Assuntos
Adesivos/farmacologia , Biomimética , Adesão Celular/efeitos dos fármacos , Propriedades de Superfície/efeitos dos fármacos , Adesivos/química , Adsorção/efeitos dos fármacos , Alquinos/química , Catecóis/química , Catecóis/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Conformação Molecular , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Compostos de Sulfidrila/química , Compostos de Sulfidrila/farmacologia
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