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1.
Mol Pharm ; 21(4): 1609-1624, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38412451

RESUMO

Cannabidiol (CBD) is the most relevant nonpsychostimulant phytocompound found in Cannabis sativa. CBD has been extensively studied and has been proposed as a therapeutic candidate for neuroinflammation-related conditions. However, being a highly lipophilic drug, it has several drawbacks for pharmaceutical use, including low solubility and high permeability. Synthetic polymers can be used as drug delivery systems to improve CBD's stability, half-life, and biodistribution. Here, we propose using a synthetic polymer as a nanoparticulate vehicle for CBD (NPCBD) to overcome the pharmacological drawbacks of free drugs. We tested the NPCBD-engineered system in the context of ischemic events in a relevant oxygen and glucose deprivation (OGD) model in primary cortical cells (PCC). Moreover, we have characterized the inflammatory response of relevant cell types, such as THP-1 (human monocytes), HMC3 (human microglia), and PCC, to NPCBD and observed a shift in the inflammatory state of the treated cells after the ischemic event. In addition, NPCBD exhibited a promising ability to restore mitochondrial function after OGD insult in both HMC3 and PCC cells at low doses of 1 and 0.2 µM CBD. Taken together, these results suggest the potential for preclinical use.


Assuntos
Canabidiol , Humanos , Canabidiol/uso terapêutico , Canabidiol/farmacologia , Doenças Neuroinflamatórias , Distribuição Tecidual , Encéfalo , Oxigênio
2.
Artigo em Inglês | MEDLINE | ID: mdl-37566441

RESUMO

Ischemic heart disease is one of the leading causes of death worldwide. The efficient delivery of therapeutic growth factors could counteract the adverse prognosis of post-myocardial infarction (post-MI). In this study, a collagen hydrogel that is able to load and appropriately deliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physically coupled with a compact collagen membrane in order to provide the suture strength required for surgical implantation. This bilayer collagen-on-collagen scaffold (bCS) showed the suitable physicochemical properties that are needed for efficient implantation, and the scaffold was able to deliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release and a lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integration of the scaffold into the heart after implantation and biocompatibility with the tissue, with a prevalence of anti-inflammatory and pro-angiogenic macrophages, as well as evidence of revascularization and improved cardiac function after 60 days. Moreover, the beneficial effect of the released SDF1 on heart remodeling was confirmed by a significant reduction in cardiac tissue stiffness. Our findings demonstrate that this multimodal scaffold is a desirable matrix that can be used as a drug delivery system and a scaffolding material to promote functional recovery after MI.

3.
Biomaterials ; 286: 121585, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35623267

RESUMO

Among all the biological entities involved in the immune response, galectins, a family of glycan-binding proteins, have been described as key in immune cell homeostasis and modulation. More importantly, only some galectin family members are crucial in the resolution of inflammation, while others perpetuate the immune response in a pathological context. As they are expressed in most major diseases, their potential as targets for new therapies seems promising. Most of the galectin family members' ubiquitous expression points to the need for targeted treatments to ensure effectiveness. Engineered biomaterials are emerging as a promising method to improve galectin-targeted strategies' therapeutic performance. In this review, we provide an overview of the role of galectins in health and disease and their potential as therapeutic targets, as well as the state-of-the-art and future directions of galectin-targeted biomaterials.


Assuntos
Materiais Biocompatíveis , Galectinas , Galectinas/metabolismo , Galectinas/uso terapêutico , Humanos , Inflamação , Polissacarídeos/metabolismo
4.
Trends Mol Med ; 28(4): 270-289, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35120836

RESUMO

The importance of glycosylation (post-translational attachment of glycan residues to proteins) in the context of neuroinflammation is only now beginning to be understood. Although the glycome is challenging to investigate due to its complexity, this field is gaining interest because of the emergence of novel analytical methods. These investigations offer the possibility of further understanding the molecular signature of disorders with underlying neuroinflammatory cascades. In this review, we portray the clinically relevant trends in glyconeurobiology and suggest glyco-related paths that could be targeted therapeutically to decrease neuroinflammation. A combinatorial insight from glycobiology and neurology can be harnessed to better understand neuroinflammatory-related conditions to identify relevant molecular targets.


Assuntos
Doenças Neuroinflamatórias , Polissacarídeos , Glicosilação , Humanos , Polissacarídeos/metabolismo , Processamento de Proteína Pós-Traducional
5.
Carbohydr Polym ; 200: 321-331, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30177172

RESUMO

Shrimp fishing industry wastes are still a main problem with high environmental impact worldwide. In this study, chitosan with ultra-high molecular weight and deacetylation degree ≥85% was obtained from shrimp fishing industry waste from Argentinean Patagonia. Chitosan based microparticles capable to entrap salicylic acid, a phytohormone known to play major role in the regulation of plant defense response against various pathogens, were prepared using TPP as crosslinker. Unloaded microparticles and microparticles loading several salicylic acid amount were fully characterized exhibiting a size between 1.57 µm and 2.45 µm. Furthermore, a good PDI, entrappment efficiencies from 59% to 98% and salicylic acid sustained release over 24 h were achieved. Chitosan based microparticles were non toxic in most of the doses applied in lettuce seedlings. Instead, microparticles can positively modulate plant growth and have the potential to improve plant defense responses. In particular salicylic acid loaded microparticles effect was very promising for its application as activators of salicylic acid dependent plant defense responses in lettuce as a model of horticultural plant species.

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