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1.
J Biomed Mater Res A ; 108(6): 1380-1389, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32105397

RESUMO

Spinal cord injury (SCI) is a central nervous disorder that can result in permanent motor and sensory damage due to a severed communication pathway. Although there is currently no effective treatment, nerve guide tubes have been used to bridge the injured stumps and act as drug delivery systems. In this study, biosynthesized cellulose (BC) nerve guides were prepared, and nerve growth factor (NGF)-a model growth factor-was incorporated into the tubular nerve guide in order to obtain a nerve guide/drug delivery system to assist the regeneration. To achieve this, Gluconacetobacter hansenii was cultivated in a special bioreactor to produce biosynthesized cellulose tubes (BCTs) in situ, and the physical and mechanical properties of the BCTs obtained from different cultivation time points were evaluated. Our results showed that the properties of the BCTs were comparable to those of the native human neural tissues, and that the NGF released from the BCTs was bioactive for at least 7 days as evaluated by PC12 cell cultures in vitro. In summary, this study evaluated the use of BCT as a drug releasing nerve guide, and our results showed that the BCT is an attractive strategy to enhance nerve regeneration after the SCI.


Assuntos
Celulose/química , Regeneração Tecidual Guiada , Fator de Crescimento Neural/administração & dosagem , Traumatismos da Medula Espinal/terapia , Alicerces Teciduais/química , Acetobacteraceae/química , Acetobacteraceae/citologia , Acetobacteraceae/metabolismo , Animais , Reatores Biológicos , Celulose/metabolismo , Sistemas de Liberação de Medicamentos , Fator de Crescimento Neural/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Células PC12 , Ratos
2.
Eur J Med Chem ; 96: 504-18, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25951294

RESUMO

Tubulin-interacting agents, like vinca alkaloid and taxanes, play a fundamental role in cancer chemotherapy, making cellular microtubules (MT), one of the few validated anticancer targets. Cancer resistance to classical MT inhibitors has motivated the development of novel molecules with increased efficacy and lower toxicity. Aiming at designing structurally-simple inhibitors of MT assembly, we synthesized a series of thirty-one 3,4,5-trimethoxy-hydrazones and twenty-five derivatives or analogs. Docking simulations suggested that a representative N-acylhydrazone could adopt an appropriate stereochemistry inside the colchicine-binding domain of tubulin. Several of these compounds showed anti-leukemia effects in the nanomolar concentration range. Interference with MT polymerization was validated by the compounds' ability to inhibit MT assembly at the biochemical and cellular level. Selective toxicity investigations done with the most potent compound, a 3,4,5-trimethoxy-hydrazone with a 1-naphthyl group, showed remarkably selective toxicity against leukemia cells in comparison with stimulated normal lymphocytes, and no acute toxicity in vivo. Finally, this molecule was as active as vincristine in a murine model of human acute lymphoblastic leukemia at a weekly dose of 1 mg/kg.


Assuntos
Anisóis/farmacologia , Antineoplásicos/farmacologia , Hidrazonas/farmacologia , Microtúbulos/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Animais , Anisóis/síntese química , Anisóis/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Microtúbulos/metabolismo , Modelos Moleculares , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Células Tumorais Cultivadas
3.
Mater Sci Eng C Mater Biol Appl ; 33(8): 4739-45, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24094182

RESUMO

Bacterial cellulose (BC) produced by Gluconacetobacter hansenii is a suitable biopolymer for biomedical applications. In order to modulate the properties of BC and expand its use as substrate for tissue engineering mainly in the form of biomembranes, glucose or dextrin were added into a BC fermentation mannitol-based medium (BCGl and BCDe, respectively) under static culture conditions. SEM images showed effects on fiber density and porosity on both sides of the BC membranes. Both enriched media decreased the BET surface area, water holding capacity, and rehydration rate. Fourier transform infrared (attenuated total reflectance mode) spectroscopy (FTIR-ATR) analysis revealed no change in the chemical structure of BC. L929 fibroblast cells were seeded on all BC-based membranes and evaluated in aspects of cell adhesion, proliferation and morphology. BCG1 membranes showed the highest biological performance and hold promise for the use in tissue engineering applications.


Assuntos
Celulose/química , Meios de Cultura/química , Dextrinas/química , Glucose/química , Manitol/química , Membranas Artificiais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Celulose/metabolismo , Meios de Cultura/farmacologia , Fibroblastos/citologia , Gluconacetobacter/efeitos dos fármacos , Gluconacetobacter/crescimento & desenvolvimento , Gluconacetobacter/metabolismo , Humanos , Porosidade
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