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1.
Chem Pharm Bull (Tokyo) ; 67(8): 877-883, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366836

RESUMO

The 4-vinylpyrimidin-2-one nucleoside (T-vinyl) forms a cross-link with the RNA containing uracil at the complementary site at a high reaction rate. To obtain the stable T-vinyl derivative so that its reactivity is protected until it access to the target site, several derivatives were investigated, and the 2-thiopyridinyl- and 2-thiopyrimidinyl T-vinyl derivatives were determined to be good candidates. The 2-thiopyrimidinyl T-vinyl derivative was found to more efficiently cross-link with mRNA albeit having a better stability than the 2-thiopyridinyl T-vinyl derivative. The investigation using the luciferase (Luc) mRNA, the synthetic mRNA and non-cellular translation system revealed that the translation is terminated at the end of the cross-linked duplex between the mRNA and the oligoribonucleotide (ORN). Thus, the 2-thiopyrimidinyl T-vinyl derivative has successfully demonstrated both a good stability and high efficiency for the cross-linking reaction, and expanded its applicability in biological applications.


Assuntos
Reagentes para Ligações Cruzadas/química , Nucleosídeos/química , Oligorribonucleotídeos/química , RNA Mensageiro/química , Compostos de Vinila/química , Reagentes para Ligações Cruzadas/síntese química , Estrutura Molecular , Nucleosídeos/síntese química , Compostos de Vinila/síntese química
2.
Molecules ; 24(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288497

RESUMO

Fungicide is used to control fungal disease by destroying and inhibiting the fungus or fungal spores that cause the disease. However, failure to deliver fungicide to the disease region leads to ineffectiveness in the disease control. Hence, in the present study, nanotechnology has enabled the fungicide active agents (hexaconazole) to be encapsulated into chitosan nanoparticles with the aim of developing a fungicide nanodelivery system that can transport them more effectively to the target cells (Ganoderma fungus). A pathogenic fungus, Ganoderma boninense (G. boninense), is destructive to oil palm whereby it can cause significant loss to oil palm plantations located in the Southeast Asian countries, especially Malaysia and Indonesia. In regard to this matter, a series of chitosan nanoparticles loaded with the fungicide, hexaconazole, was prepared using various concentrations of crosslinking agent sodium tripolyphosphate (TPP). The resulting particle size revealed that the increase of the TPP concentration produced smaller particles. In addition, the in vitro fungicide released at pH 5.5 demonstrated that the fungicide from the nanoparticles was released in a sustainable manner with a prolonged release time up to 86 h. On another note, the in vitro antifungal studies established that smaller particle size leads to lower half maximum effective concentration (EC50) value, which indicates higher antifungal activity against G. boninense.


Assuntos
Arecaceae/microbiologia , Quitosana/química , Portadores de Fármacos/química , Fungicidas Industriais/farmacologia , Ganoderma/efeitos dos fármacos , Nanopartículas/química , Doenças das Plantas/microbiologia , Triazóis/farmacologia , Reagentes para Ligações Cruzadas/química , Liberação Controlada de Fármacos , Cinética , Tamanho da Partícula , Polifosfatos/química
3.
J Microbiol Biotechnol ; 29(7): 1078-1082, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31280528

RESUMO

Poly-γ-glutamate (γ-PGA) has various applications due to its desirable characteristics in terms of safety and biodegradability. Previous studies have been conducted on γ-PGA hydrogels produced by γ-ray irradiation, but these hydrogels have proved unstable in solutions. This study was conducted to enable the γ-PGA hydrogel to maintain a stable form in solutions. The γ-PGA mixture for UV-irradiation was prepared with a cross-linker (N,N,N-trimethyl-3-[(2- methylacryloyl)amino]propan-1-aminium). Both γ-PGA hydrogels' characteristics, including stability in solutions, were examined. The UV-irradiated γ-PGA hydrogel maintained a stable form during the nine weeks of the study, but the γ-ray irradiated hydrogel dissolved after one week.


Assuntos
Raios gama , Hidrogéis/química , Ácido Poliglutâmico/análogos & derivados , Raios Ultravioleta , Materiais Biocompatíveis/química , Reagentes para Ligações Cruzadas/química , Hidrogéis/síntese química , Concentração de Íons de Hidrogênio , Ácido Poliglutâmico/química , Soluções , Viscosidade
4.
Pharm Res ; 36(9): 127, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236836

RESUMO

PURPOSE: Paclitaxel (PTX)-loaded genipin-crosslinked gelatin microspheres (GP-MS) are a prolonged IP delivery system under development for the treatment of peritoneal minimal residual disease (pMRD). Here, we show the use of a pharmacokinetic-pharmacodynamic (PKPD) modelling approach to inform the formulation development of PTX-GP-MS in a mice pMRD model. METHODS: PTX blood concentrations and survival data were obtained in Balb/c Nu mice receiving different single IP doses (7.5 and/or 35 mg/kg) of PTX-ethanolic loaded GP-MS (PTXEtOH-GP-MS), PTX-nanosuspension loaded GP-MS (PTXnano-GP-MS), and immediate release formulation Abraxane®. A population PK model was developed to characterize the PTX blood concentration pattern and to predict PTX concentrations in peritoneum. Afterwards, PKPD relationships between the predicted peritoneal or blood concentrations and survival were explored using time-to-event modelling. RESULTS: A PKPD model was developed that simultaneously describes the competing effects of treatment efficacy (driven by peritoneal concentration) and toxicity (driven by blood concentration) of PTX on survival. Clear survival advantages of PTXnano-GP-MS over PTXEtOH-GP-MS and Abraxane® were found. Simulations of different doses of PTXnano-GP-MS demonstrated that drug-induced toxicity is high at doses between 20 and 35 mg/kg. CONCLUSIONS: The model predicts that the dose range of 7.5-15 mg/kg of PTXnano-GP-MS provides an optimal balance between efficacy and safety.


Assuntos
Paclitaxel Ligado a Albumina/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Peritoneais/tratamento farmacológico , Paclitaxel Ligado a Albumina/química , Paclitaxel Ligado a Albumina/farmacocinética , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Linhagem Celular Tumoral , Reagentes para Ligações Cruzadas/química , Portadores de Fármacos , Gelatina/química , Humanos , Iridoides/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Microesferas , Modelos Biológicos , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Int J Nanomedicine ; 14: 3893-3909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239663

RESUMO

Background: Photothermal and chemotherapy treatment has been frequently studied for cancer therapy; however, chemotherapy is equally toxic to both normal and cancer cells. The clinical application value of most kinds of photothermal transforming agents remains limited, due to their poor degradation and minimal accumulation in tumors. Materials and methods: We reported the synthesis of photothermal transforming agents (MoS2) and chemotherapeutic (doxorubicin, DOX) co-loaded electrospun nanofibers using blend electrospinning for the treatment of postoperative tumor recurrence. Results: Under the irradiation of an 808 nm laser, the as-prepared chitosan/polyvinyl alcohol/MoS2/DOX nanofibers showed an admirable photothermal conversion capability with a photothermal conversion efficiency of 23.2%. These composite nanofibers are in vitro and in vivo biocompatible. In addition, they could control the sustained release of DOX and the generated heat can sensitize the chemotherapeutic efficacy of DOX via enhancing its release rate. Their chemo-/photothermal combined therapy efficiency was systematically studied in vitro and in vivo. Instead of circulating with the body fluid, MoS2 was trapped by the nanofibrous matrix in the tumor and so its tumor-killing ability was not compromised, thus rendering this composite nanofiber a promising alternative for future clinical translation within biomedical application fields. Conclusion: Chitosan/polyvinyl alcohol/MoS2/DOX nanofibers showed an excellent photothermal conversion capability with a photothermal conversion efficiency of 23.2% and can completely inhibit the postoperative tumor reoccurrence.


Assuntos
Dissulfetos/química , Doxorrubicina/uso terapêutico , Molibdênio/química , Nanofibras/química , Nanotecnologia/métodos , Neoplasias/terapia , Fototerapia , Animais , Materiais Biocompatíveis/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HT29 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanofibras/ultraestrutura , Recidiva Local de Neoplasia/patologia , Neoplasias/sangue , Neoplasias/patologia , Neoplasias/cirurgia , Padrões de Referência , Resultado do Tratamento
6.
Anal Chim Acta ; 1074: 131-141, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159933

RESUMO

Semiconducting single-walled carbon nanotubes (s-SWCNTs) have been demonstrated as an excellent material for transistors, miniaturized devices and sensors due to their high carrier mobility, stability, scattering-free ballistic transport of carriers etc. Herein, we have designed a biosensor to selectively detect methyl parathion (MP, organophosphorus pesticide) using glutaraldehyde (Glu) cross-linked with acetylcholinesterase (AChE) immobilized on s-SWCNTs wrapped with bovine serum albumin (BSA). The fabricated biosensor was characterized and confirmed by Fourier-transform infrared spectroscopy (FT-IR), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). In the presence of MP, the effective interaction between AChE and MP favours the accumulation of MP-AChE complex on the glassy carbon electrode (GCE) surface which reduces the electron transfer property. Based on this interaction, detection of various concentration of MP was demonstrated by SWV using BSA/AChE-Glu-s-SWCNTs composite modified electrode. The proposed biosensor exhibited a wide linear range (WLR) for MP target in 100 mM phosphate buffered saline solution (PBS) (pH 7.4) from 1 × 10-10 M to 5 × 10-6 M with a limit of detection (LOD) of 3.75 × 10-11 M. In addition, the BSA/AChE-Glu-s-SWCNTs/GCE biosensor showed good repeatability and reproducibility for MP detection. Moreover, the proposed biosensor showed better electrode stability when stored at 4 °C. This new electrochemical biosensor is also exhibited high selectivity and sensitivity for MP, which made it possible to test MP in real strawberry and apple juices. Furthermore, the BSA/AChE-Glu-s-SWCNTs/GCE offered a favourable electron transfer between the acetylthiocholine chloride (ATCl) and electrode interface than BSA/AChE-s-SWCNTs/GCE, s-SWCNTs/GCE and bare GCE.


Assuntos
Acetilcolinesterase/química , Inseticidas/análise , Metil Paration/análise , Nanocompostos/química , Nanotubos de Carbono/química , Soroalbumina Bovina/química , Animais , Técnicas Biossensoriais/métodos , Carbono , Bovinos , Reagentes para Ligações Cruzadas/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Electrophorus , Enzimas Imobilizadas/química , Contaminação de Alimentos/análise , Fragaria/química , Glutaral/química , Inseticidas/química , Limite de Detecção , Malus/química , Metil Paration/química , Reprodutibilidade dos Testes
7.
Int J Nanomedicine ; 14: 3361-3373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190797

RESUMO

Purpose: To fabricate multifunctional nanocapsule via Pickering emulsion route to facilitate tumor-targeted delivery. Methods: Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles (PNA) stabilized nanocapsules were fabricated by Pickering emulsion (PE) technology. For controllable drug-release and enhancing targeted antitumor effects, the nanocapsules were crosslinked with cystamine and coupled on cell-surface molecule markers (cRGDfK) to achieve on-demand drug release and targeted delivery. Results: The fabricated PE and nanocapsules with average particle sizes (250 and 150 nm) were obtained. Encapsulation efficiency of hydrophobic anticancer drug (DOX) was determined as >90%. Release kinetic profiles for encapsulated nanocapsules displayed circulation stability and redox-sensitive releasing behavior with the supposed increase bioavailability. Both cytotoxicity assay, cellular uptake analysis and anticancer efficacy in B16F10 murine model demonstrated these redox-responsive drug-release and active targeted delivery. Conclusion: The results clearly demonstrated nanocapsule via PE route as promising candidate to provide an effective platform for incorporating hydrophobic drug for targeted cancer chemotherapy.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Nanocápsulas/química , Neoplasias/tratamento farmacológico , Peptídeos Cíclicos/química , Resinas Acrílicas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular , Reagentes para Ligações Cruzadas/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanocápsulas/ultraestrutura , Oxirredução , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoimina/química
8.
Nat Commun ; 10(1): 2626, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201308

RESUMO

Chromatin of mammalian nucleus folds into discrete contact enriched regions such as Topologically Associating Domains (TADs). Folding hierarchy and internal organization of TADs is highly dynamic throughout cellular differentiation, and are correlated with gene activation and silencing. To account for multiple interacting TADs, we developed a parsimonious randomly cross-linked (RCL) polymer model that maps high frequency Hi-C encounters within and between TADs into direct loci interactions using cross-links at a given base-pair resolution. We reconstruct three TADs of the mammalian X chromosome for three stages of differentiation. We compute the radius of gyration of TADs and the encounter probability between genomic segments. We found 1) a synchronous compaction and decompaction of TADs throughout differentiation and 2) high order organization into meta-TADs resulting from weak inter-TAD interactions. Finally, the present framework allows to infer transient properties of the chromatin from steady-state statistics embedded in the Hi-C/5C data.


Assuntos
Diferenciação Celular/genética , Montagem e Desmontagem da Cromatina , Cromatina/metabolismo , Polímeros/química , Cromossomo X/metabolismo , Animais , Reagentes para Ligações Cruzadas/química , Sequenciamento de Nucleotídeos em Larga Escala , Modelos Moleculares , Conformação de Ácido Nucleico
9.
Nat Commun ; 10(1): 2682, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31213602

RESUMO

RNA-protein complexes play essential regulatory roles at nearly all levels of gene expression. Using in vivo crosslinking and RNA capture, we report a comprehensive RNA-protein interactome in a metazoan at four levels of resolution: single amino acids, domains, proteins and multisubunit complexes. We devise CAPRI, a method to map RNA-binding domains (RBDs) by simultaneous identification of RNA interacting crosslinked peptides and peptides adjacent to such crosslinked sites. CAPRI identifies more than 3000 RNA proximal peptides in Drosophila and human proteins with more than 45% of them forming new interaction interfaces. The comparison of orthologous proteins enables the identification of evolutionary conserved RBDs in globular domains and intrinsically disordered regions (IDRs). By comparing the sequences of IDRs through evolution, we classify them based on the type of motif, accumulation of tandem repeats, conservation of amino acid composition and high sequence divergence.


Assuntos
Evolução Molecular , Proteômica/métodos , Motivos de Ligação ao RNA/genética , Proteínas de Ligação a RNA/genética , RNA/metabolismo , Sequência de Aminoácidos/genética , Animais , Linhagem Celular , Sequência Conservada/genética , Reagentes para Ligações Cruzadas/química , Drosophila , Humanos , Peptídeos/química , Peptídeos/genética , Ligação Proteica/genética , Proteoma/genética , RNA/química , Proteínas de Ligação a RNA/química
10.
Nat Commun ; 10(1): 2765, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235691

RESUMO

G protein-coupled receptors (GPCRs) can integrate extracellular signals via allosteric interactions within dimers and higher-order oligomers. However, the structural bases of these interactions remain unclear. Here, we use the GABAB receptor heterodimer as a model as it forms large complexes in the brain. It is subjected to genetic mutations mainly affecting transmembrane 6 (TM6) and involved in human diseases. By cross-linking, we identify the transmembrane interfaces involved in GABAB1-GABAB2, as well as GABAB1-GABAB1 interactions. Our data are consistent with an oligomer made of a row of GABAB1. We bring evidence that agonist activation induces a concerted rearrangement of the various interfaces. While the GB1-GB2 interface is proposed to involve TM5 in the inactive state, cross-linking of TM6s lead to constitutive activity. These data bring insight for our understanding of the allosteric interaction between GPCRs within oligomers.


Assuntos
Modelos Moleculares , Domínios Proteicos/fisiologia , Multimerização Proteica/fisiologia , Receptores de GABA-B/metabolismo , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/fisiologia , Sítio Alostérico/efeitos dos fármacos , Sítio Alostérico/fisiologia , Reagentes para Ligações Cruzadas/química , Agonistas dos Receptores de GABA-B/farmacologia , Células HEK293 , Humanos , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Domínios Proteicos/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo
11.
Chem Pharm Bull (Tokyo) ; 67(6): 505-518, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155555

RESUMO

Nucleic acid therapeutics such as antisense and small interfering RNA (siRNA) have attracted increasing attention as innovative medicines that interfere with and/or modify gene expression systems. We have developed new functional oligonucleotides that can target DNA and RNA with high efficiency and selectivity. This review summarizes our achievements, including (1) the formation of non-natural triplex DNA for sequence-specific inhibition of transcription; (2) artificial receptor molecules for 8-oxidized-guanosine nucleosides; and (3) reactive oligonucleotides with a cross-linking agent or a functionality-transfer nucleoside for RNA pinpoint modification.


Assuntos
DNA/química , RNA/química , Reagentes para Ligações Cruzadas/química , DNA/metabolismo , DNA/farmacologia , Humanos , Nucleosídeos/análogos & derivados , Nucleosídeos/farmacologia , Oligonucleotídeos/química , Oligonucleotídeos/metabolismo , Polietilenoglicóis/química , RNA/metabolismo , Telomerase/genética , Telomerase/metabolismo , Transcrição Genética/efeitos dos fármacos
12.
Food Chem ; 297: 124972, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253320

RESUMO

The aim of the present study was to evaluate Paralichthys olivaceus parvalbumin (PV) following treatment by laccase (LAC) in the presence of propyl gallate (PG) on the structure and potential allergenicity. The structure of LAC + PG treated PV was analyzed through SDS-PAGE, CD, fluorescence, and allergenicity was analyzed by immunological and cell model. Our results showed that LAC + PG treatment can induce structural changes through PV cross-linking. Western blotting and indirect ELISA analysis revealed the decrease in IgG binding capacity of PV, corresponding with the structural changes. The results of in vitro digestion illustrate that LAC + PG treated PV showed more resistance to gastrointestinal digestion compared to untreated PV. The release rate of ß-hexosaminidase and histamine decreased by 35.6% and 66.9%, respectively, with LAC + PG treatment by RBL-2H3 cell assay. Considering the wide utilization of LAC in food industry, our treatment reveals its potential for creation of hypoallergenic fish products under mild reaction conditions.


Assuntos
Alérgenos/imunologia , Proteínas de Peixes/imunologia , Linguados/imunologia , Lacase/metabolismo , Parvalbuminas/imunologia , Galato de Propila/química , Animais , Catálise , Reagentes para Ligações Cruzadas/química , Digestão , Ensaio de Imunoadsorção Enzimática , Proteínas de Peixes/química , Indústria Alimentícia , Histamina/metabolismo , Parvalbuminas/química , beta-N-Acetil-Hexosaminidases/metabolismo
13.
Nat Commun ; 10(1): 2223, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31110174

RESUMO

Mammalian cells are different from plant and microbial cells, having no exterior cell walls for protection. Environmental assaults can easily damage or destroy mammalian cells. Thus, the ability to develop a biomimetic cell wall (BCW) on their plasma membrane as a shield can advance various applications. Here we demonstrate the synthesis of BCW with a framing template and a crosslinked matrix for shielding live mammalian cells. The framing template is a supramolecular DNA structure. The crosslinked matrix is a polyelectrolyte complex made of alginate and polylysine. As the entire procedure of BCW synthesis is strictly operated under physiological conditions, BCW-covered mammalian cells can maintain high bioactivity. More importantly, the data show that BCW can shield live mammalian cells from not only physical assaults but also biological assaults. Thus, this study has successfully demonstrated the synthesis of BCW on live mammalian cells with great potential of shielding them from environmental assaults.


Assuntos
Materiais Biomiméticos/metabolismo , Parede Celular/metabolismo , DNA/metabolismo , Nanocápsulas/química , Alginatos/química , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Parede Celular/ultraestrutura , Reagentes para Ligações Cruzadas/química , Humanos , Microscopia Eletrônica de Transmissão , Nanocápsulas/ultraestrutura , Polilisina/química
14.
Anal Bioanal Chem ; 411(15): 3269-3280, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31037371

RESUMO

A new electrode based on glassy carbon modified with an alginate film cross-linked with glutaraldehyde containing immobilized carbon black particles was successfully developed and applied for the determination of paraquat (PQ), a herbicide widely used for broadleaf weed control. Different polysaccharides (alginate, cellulose, pectin, starch, and chitosan) were investigated for the immobilization process, and alginate presented the highest chemical modifier potential for PQ determination. Additionally, the influence of chemical cross-linking agents (glutaraldehyde and epichlorohydrin) on the morphology, electrochemical response, and film stability was investigated. All experimental conditions were optimized, including the supporting electrolyte conditions (composition, pH, and concentration) and square wave voltammetry technical parameters. Under the optimized experimental conditions, the PQ analytical curve was linear from 0.4 to 2.0 mg L-1 and the limits of detection and quantification were 0.06 and 0.19 mg L-1, respectively. The proposed electrode is easy to obtain, stable, selective, sensitive, and low cost and was successfully applied for PQ determination in environmental and beverage samples. Graphical abstract.


Assuntos
Alginatos/química , Bebidas/análise , Carbono/química , Técnicas Eletroquímicas/instrumentação , Herbicidas/análise , Paraquat/análise , Poluentes Químicos da Água/análise , Reagentes para Ligações Cruzadas/química , Eletrodos , Monitoramento Ambiental/instrumentação , Análise de Alimentos/instrumentação , Limite de Detecção , Fuligem/química , Água/análise
15.
Carbohydr Polym ; 216: 45-53, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047081

RESUMO

Herein the construction of a strong gelatin hydrogel is presented by using pullulan dialdehyde (PDA) as a macromolecular crosslinker. The resultant PDA crosslinked gelatin hydrogels (G-PDA) exhibit extremely high mechanical strength, manifested in the achieved optimal compressive stress of 5.80 MPa at 80% strain, which is up to 152 times higher than pure gelatin hydrogel. The G-PDA were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The extent of crosslinking was determined by ninhydrin assay. The results suggested that the synergistic effect of dual-crosslinking, which is composed of short- and long-range covalent crosslinking and thermoreversible physical crosslinking, may played a key role in enhancing the load-bearing capacity of ensuing hydrogels. The swelling and enzymatic degradation of G-PDA are gradually limited with increasing PDA concentration. The result from MTT assay demonstrated that G-PDA is non-cytotoxic against MC3T3 cells, regardless of the concentrations of PDA.


Assuntos
Aldeídos/química , Materiais Biocompatíveis/química , Reagentes para Ligações Cruzadas/química , Gelatina/química , Glucanos/química , Hidrogéis/química , Aldeídos/síntese química , Aldeídos/toxicidade , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , Linhagem Celular , Colagenases/química , Força Compressiva , Reagentes para Ligações Cruzadas/síntese química , Reagentes para Ligações Cruzadas/toxicidade , Módulo de Elasticidade , Gelatina/síntese química , Gelatina/toxicidade , Glucanos/síntese química , Glucanos/toxicidade , Hidrogéis/síntese química , Hidrogéis/toxicidade , Hidrólise , Camundongos , Oxirredução , Ácido Periódico/química , Porosidade
16.
Carbohydr Polym ; 216: 63-71, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047083

RESUMO

The effect of hydrazide linkers on the formation and mechanical properties of hyaluronan hydrogels was intensively evaluated. The reaction kinetics of hydrazone formation was monitored by NMR spectroscopy under physiological conditions where polyaldehyde hyaluronan (unsaturated: ΔHA-CHO, saturated: HA-CHO) was reacted with various hydrazides to form hydrogels. Linear (adipic, oxalic dihydrazide) and branched (N,N´,N´´-tris(hexanoylhydrazide-6-yl)phosphoric triamide and 4-arm-PEG hydrazide) hydrazides were compared as crosslinking agents. The mechanical properties of hydrogels were also modified by attaching a hydrophobic chain to HA-CHO; however, it was found that this modification did not lead to an increase in hydrogel stiffness. Cytotoxicity tests showed that all tested hydrazide crosslinkers reduced the viability of cells only slightly, and that the final hyaluronan hydrogels were non-toxic materials.


Assuntos
Reagentes para Ligações Cruzadas/química , Ácido Hialurônico/análogos & derivados , Hidrazinas/química , Hidrazonas/química , Hidrogéis/química , Acilação , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Reagentes para Ligações Cruzadas/síntese química , Reagentes para Ligações Cruzadas/toxicidade , Módulo de Elasticidade , Ácido Hialurônico/síntese química , Ácido Hialurônico/toxicidade , Hidrazinas/síntese química , Hidrazinas/toxicidade , Hidrazonas/síntese química , Hidrazonas/toxicidade , Hidrogéis/síntese química , Hidrogéis/toxicidade , Concentração de Íons de Hidrogênio , Cinética , Camundongos , Células Swiss 3T3
17.
Eur J Pharm Sci ; 135: 60-67, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31108205

RESUMO

In this study, we assessed the feasibility of using digital light processing (DLP) 3D printers (3DP) in fabrication of solid oral dosage forms. The DLP technology uses a digital micromirror device (DMD) that reflects and focuses ultraviolet (UV) light on the surfaces of photoreactive materials that polymerize in a layer-by-layer fashion. Using poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) dimethacrylate (PEGDMA) as photoreactive polymers and theophylline as a model drug, we deployed a DLP printer to fabricate tablets. After optimizing various printing parameters including UV intensity and exposure time, layer thickness, and polymer concentration, we printed various types of tablets with and without perforation. We then assessed the tablets for drug content, mechanical strengths, swellability, weight variation, microscopic features, drug-polymer interactions and drug release profiles. The loading of theophylline was 1%, which was independent of tablet weights. The drug content and weight variation were within the acceptable range, as recommended by the United States Pharmacopeia (USP). Scanning electronic microscopic (SEM) pictures showed tablets with distinct layers and smooth outer surfaces. The spectral scans, obtained using Fourier Transform Infrared Spectroscopy (FTIR), showed no chemical interactions between the drug and polymers. Similarly, drug content determined using a UV spectrophotometer was the same as that determined by a high performance liquid chromatography (UPLC). The extent of drug release increased with the increase in the number of perforations in the tablets. Overall, this study demonstrates that DLP 3DP can be used as a platform for fabricating oral tablets with well-defined shapes and different release profiles.


Assuntos
Portadores de Fármacos/química , Metacrilatos/química , Processos Fotoquímicos , Polietilenoglicóis/química , Impressão Tridimensional , Comprimidos/química , Reagentes para Ligações Cruzadas/química , Liberação Controlada de Fármacos , Excipientes/química , Tamanho da Partícula , Solubilidade , Tecnologia Farmacêutica , Teofilina/administração & dosagem , Raios Ultravioleta
18.
Adv Mater ; 31(27): e1808233, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31081156

RESUMO

Microcapsules are often used as individually dispersed carriers of active ingredients to prolong their shelf life or to protect premature reactions with substances contained in the surrounding. This study goes beyond this application and employs microcapsules as principal building blocks of macroscopic 3D materials with well-defined granular structures. To achieve this goal and inspired by nature, capsules are fabricated from block-copolymer surfactants that are functionalized with catechols, a metal-coordinating motive. These surfactants self-assemble at the surface of emulsion drops where they are ionically cross-linked to form viscoelastic capsules that display a low permeability even toward small encapsulants. It is demonstrated that the combination of the mechanical strength, flexibility, and stickiness of the capsules enables their additive manufacturing into macroscopic granular structures. Thereby, they open up new opportunities for 3D printing of soft, self-healing materials composed of individual compartments that can be functionalized with different types of spatially separated reagents.


Assuntos
Cápsulas/química , Tensoativos/química , Catecóis/química , Complexos de Coordenação/química , Reagentes para Ligações Cruzadas/química , Fluorcarbonetos/química , Ferro/química , Fenômenos Mecânicos , Permeabilidade , Polímeros/química , Impressão Tridimensional , Propilenoglicóis/química
19.
Carbohydr Polym ; 217: 160-167, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31079673

RESUMO

Polysaccharides can be modified by reactive functional groups to enable chemical crosslinking. We studied how different methods of crosslinking methacrylate-functionalized chitosan affected the network structures and various properties relevant for utilization of the chemically crosslinked hydrogels in biomedical applications, including tissue engineering and delivery of therapeutic agents. Four chitosan hydrogels were made by either the free radical polymerization with varying initiation kinetics and an addition of chain transfer agents or the based-catalyzed Michael-type addition reaction. Four chitosan hydrogels having identical polymer fractions at equilibrium swelling exhibited marked differences in shear moduli, dextran diffusion rate, and especially enzymatic degradation behaviors. Hydrogels made by the free radical polymerization with no chain transfer agent were highly resistant to complete degradation by enzyme for an extended period. We inferred that such resistance originated from chain bundles characterized by densely branched networks of chitosan chains, which was determined by small-angle X-ray scattering analysis.


Assuntos
Quitosana/química , Hidrogéis/química , Quitosana/síntese química , Reagentes para Ligações Cruzadas/síntese química , Reagentes para Ligações Cruzadas/química , Dextranos/química , Difusão , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Humanos , Hidrogéis/síntese química , Hidrólise , Metacrilatos/síntese química , Metacrilatos/química , Muramidase/química , Polimerização
20.
Soft Matter ; 15(20): 4200-4207, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31070656

RESUMO

Herein, we have designed and synthesized a novel forky peptide D3F3 that transforms into a hydrogel through crosslinking induced by ZIs stimuli. We have employed D3F3 as a suitable drug carrier that is conjugated with DOX. Since the concentration of zinc ions necessary for triggering gelation falls into the physiological range present in prostate tissue, while other cationic ions fail to trigger at physiological concentrations, the peptide-based drug delivery system (DDS) is injectable and would achieve prostate tissue-specific self-assembly in situ. The D3F3 hydrogels exhibited an optimal gelation time, satisfactory mechanical strength (can be enhanced after incorporation of DOX) as well as excellent thixotropic properties. The DDS reserved some DOX in the prostate 24 h after the injection, making local sustained release possible. In addition, the peptide materials demonstrated no cytotoxicity against normal fibroblast cells and no damage was observed to the prostate tissue of rats. The drug release followed a non-Fickian diffusion model, with no burst release observed. Importantly, the DOX-hydrogel system exhibited good anti-cancer efficacy when incubated with prostate cancer cells DU-145. Therefore, this study lays the groundwork for the future design of tissue-specific DDSs that are triggered by cationic ions (e.g. zinc ions), and the platform could be further developed to incorporate other potent drugs utilized in the field of prostate cancer therapy, thereby increasing their potency and reducing their side effects.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Hidrogéis/química , Oligopeptídeos/síntese química , Neoplasias da Próstata/tratamento farmacológico , Animais , Ácido Aspártico/química , Cátions Bivalentes , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Células NIH 3T3 , Próstata , Zinco/química
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