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1.
Mol Pharm ; 17(4): 1363-1376, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32053378

RESUMO

Liquid, injectable hydrophobic polymers have advantages as degradable drug delivery vehicles; however, polymers examined for this purpose to date form acidic degradation products that may damage acid-sensitive drugs. Herein, we report on a new viscous liquid vehicle, poly(trimethylene carbonate-co-5-hydroxy-trimethylene carbonate), which degrades through intramolecular cyclization producing glycerol, carbon dioxide, and water-soluble trimethylene carbonate. Copolymer degradation durations from weeks to months were achieved with the 5-hydroxy-trimethylene carbonate (HTMC) content of the oligomer having the greatest impact on the degradation rate, with oligomers possessing a higher HTMC content degrading fastest. The degradation products were non-cytotoxic towards 3T3 fibroblasts and RAW 264.7 macrophages. These copolymers can be injected manually through standard gauge needles and, importantly, during in vitro degradation, the microenvironmental pH within the oligomers remained near neutral. Complete and sustained release of the acid-sensitive protein vascular endothelial growth factor was achieved, with the protein remaining highly bioactive throughout the release period. These copolymers represent a promising formulation for local and sustained release of acid sensitive drugs.


Assuntos
Carbonatos/química , Dioxanos/química , Preparações Farmacêuticas/química , Polímeros/química , Água/química , Células 3T3 , Animais , Dióxido de Carbono/química , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Concentração de Íons de Hidrogênio , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Fator A de Crescimento do Endotélio Vascular/metabolismo , Viscosidade
2.
Environ Sci Pollut Res Int ; 27(11): 12491-12498, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31997249

RESUMO

In this study, we estimated extracellular concentrations of algal-derived sulfur species in response to changing photoperiods. Cultures from three algal species (Chlorella vulgaris, Chlamydomonas reinhardtii, Scenedesmus obliquus) were subjected to five different light:dark cycles (12:12, 14:10, 16:8, 18:6, 20:4 h) for a period of 3 days. Sulfur compounds including total reactive thiol concentrations, electroactive reduced sulfur species (RSS), and thiol isomers were measured using qBBr fluorescence, differential pulse cathodic stripping voltammetry (DP-CSV), and high-resolution mass spectrometry (HRMS), respectively. Total reactive thiol concentrations were greater in Scenedesmus than in Chlamydomonas and Chlorella at low light regimes (i.e., 12:12 h) whereas Chlamydomonas produced more RSS than the other two species (p < 0.05) at any light regime. Scenedesmus was the only responsive species to produce maximal electroactive RSS, and HRMS equivalent thiol compounds under low light regime, congruent with previous studies. Principal component analysis revealed relationships between qBBr-equivalent thiol and GSH-equivalent RSS concentrations for Scenedesmus and Chlamydomonas (p < 0.05) suggesting that thiols were the dominant species in the pool of electroactive RSS for these two algal species. Overall, these results showed that the light growth conditions greatly influenced the production of S-rich compounds by algae, affecting the complexation of metals such as mercury and cadmium, especially during planktonic blooms.


Assuntos
Chlamydomonas reinhardtii , Chlorella vulgaris , Scenedesmus , Fotoperíodo , Enxofre
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