Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Exp Neurol ; 379: 114849, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38857748

RESUMO

Cerebral ischemic stroke is a serious disease with high mortality and disability rates. However, few neuroprotective drugs have been used for ischemic stroke in the clinic. Two main reasons may be responsible for this failure: difficulty in penetrating the blood-brain barrier (BBB) and easily inactivated in the blood circulation. Ferroptosis, a lipid oxidation-related cell death, plays significant roles in cerebral ischemia-reperfusion injury. We utilized RVG29, a peptide derived from Rabies virus glycoprotein, to obtain BBB-targeted lipid nanoparticles (T-LNPs) in order to investigate whether T-LNPs improved the neuroprotective effects of Ferrostatin-1 (Fer1, an inhibitor of ferroptosis) against cerebral ischemic damage. T-LNPs significantly increased BBB penetration following oxygen/glucose deprivation exposure in an in vitro BBB model and enhanced the fluorescence distribution in brain tissues at 6 h post-administration in a cerebral ischemic murine model. Moreover, T-LNPs encapsulated Fer1 (T-LNPs-Fer1) significantly enhanced the inhibitory effects of Fer1 on ferroptosis by maintaining the homeostasis of NADPH oxidase 4 (NOX4) and glutathione peroxidase 4 (GPX4) signals in neuronal cells after cerebral ischemia. T-LNPs-Fer1 significantly suppressed oxidative stress [heme oxygenase-1 expression and malondialdehyde (the product of lipid ROS reaction)] in neurons and alleviated ischemia-induced neuronal cell death, compared to Fer1 alone without encapsulation. Furthermore, T-LNPs-Fer1 significantly reduced cerebral infarction and improved behavior functions compared to Fer1-treated cerebral ischemic mice after 45-min ischemia/24-h reperfusion. These findings showed that the T-LNPs helped Fer1 penetrate the BBB and improved the neuroprotection of Fer1 against cerebral ischemic damage in experimental stroke, providing a feasible translational strategy for the development of clinical drugs for the treatment of ischemic stroke.


Assuntos
Barreira Hematoencefálica , Cicloexilaminas , Nanopartículas , Fármacos Neuroprotetores , Fenilenodiaminas , Animais , Camundongos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Fármacos Neuroprotetores/farmacologia , Nanopartículas/administração & dosagem , Masculino , Cicloexilaminas/farmacologia , Fenilenodiaminas/farmacologia , Fenilenodiaminas/uso terapêutico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/patologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Isquemia Encefálica/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Ferroptose/efeitos dos fármacos , Glicoproteínas , Lipossomos , Fragmentos de Peptídeos , Proteínas Virais
2.
Nanomaterials (Basel) ; 14(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38607144

RESUMO

Psoriasis, a chronic inflammatory skin disease induced by various factors, including genetic factors, immune factors, environmental factors, and psychological factors, is characterized by thickening of the epidermis, excessive proliferation of keratinocytes, abnormal differentiation, and an excessive inflammatory response. Traditional treatments for psoriasis still face challenges because of limited curative effects, notable side effects, and a tendency for recurrence. In contrast, topical therapy provides a favorable option for psoriasis treatment because of its noninvasive and self-administered method. In this study, gentiopicrin (Gen) is encapsulated in the liposomes to form a nanodrug, and then chitosan is covered on the nanodrug to assemble the nanodrug delivery system (CS@Gen), which is used as a topical agent for treating psoriasis. Then M5 (a mixture of five pro-inflammatory cytokines, i.e., IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α)-induced HacaT cells and imiquimod-induced psoriasis mouse models are established, whose results show that CS@Gen induces apoptosis and inhibits the proliferation and cell migration of psoriasis keratinocytes. Additionally, the application of CS@Gen cream can significantly reduce epidermal thickness, diminish skin scaling, and improve other related mechanisms in mice affected by psoriasis. Meanwhile, the prepared CS@Gen can significantly reduce the expression levels of IL-17a, Cxcl2, S100a, Mki67, and other related inflammatory factors, resulting in indirectly inhibiting the inflammation of keratinocytes. In summary, the present study provides an ideal loading for an anti-inflammatory and immunomodulatory drug delivery system for the treatment of psoriasis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA