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1.
Adv Healthc Mater ; 13(13): e2303016, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38431929

RESUMO

Curcumin, a natural bioactive polyphenol with diverse molecular targets, is well known for its anti-oxidation and anti-inflammatory potential. However, curcumin exhibits low solubility (<1 µg mL-1), poor tissue-targeting ability, and rapid oxidative degradation, resulting in poor bioavailability and stability for inflammatory therapy. Here, poly(diselenide-oxalate-curcumin) nanoparticle (SeOC-NP) with dual-reactive oxygen species (ROS) sensitive chemical moieties (diselenide and peroxalate ester bonds) is fabricated by a one-step synthetic strategy. The results confirmed that dual-ROS sensitive chemical moieties endowed SeOC-NP with the ability of targeted delivery of curcumin and significantly suppress oxidative degradation of curcumin for high-efficiency inflammatory therapy. In detail, the degradation amount of curcumin for SeOC is about 4-fold lower than that of free curcumin in an oxidative microenvironment. As a result, SeOC-NP significantly enhanced the antioxidant activity and anti-inflammatory efficacy of curcumin in vitro analysis by scavenging intracellular ROS and suppressing the secretion of nitric oxide and pro-inflammatory cytokines. In mouse colitis models, orally administered SeOC-NP can remarkably alleviate the symptoms of IBD and maintain the homeostasis of gut microbiota. This work provided a simple and effective strategy to fabricate ROS-responsive micellar and enhance the oxidation stability of medicine for precise therapeutic inflammation.


Assuntos
Colite , Curcumina , Nanopartículas , Espécies Reativas de Oxigênio , Curcumina/química , Curcumina/farmacologia , Animais , Colite/tratamento farmacológico , Colite/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Células RAW 264.7 , Oxirredução , Antioxidantes/química , Antioxidantes/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Masculino
2.
J Control Release ; 351: 896-906, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36202152

RESUMO

Targeted antibiotic delivery system would be an ideal solution for the treatment of enteropathogenic infections since it avoids the excessive usage of antibiotics clinically, which may lead to threat on public health and food safety. Salmonella spp. are Enteropathogens, but they are also robust H2S producers in the intestinal tracts of hosts. To this end, the PEGylated poly (α lipoic acid) (PEG-PALA) copolymer nanoparticles with hydrophilic exterior and hydrophobic interior were designated in this study to encapsulate the antibiotics and release them in response to H2S produced by Salmonella spp. The PEG-PALA nanoparticles demonstrated excellent stability in vitro and biocompatibility toward mammalian Caco-2 and 293 T cells. The release of ciprofloxacin from PEG-PALA nanoparticle was only 25.44 ± 0.57% and 26.98 ± 1.93% (w/w) in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions without H2S stimulation. However, the release amounts of ciprofloxacin were up to 73.68 ± 1.63% (w/w) in the presence of 1 mM Na2S as H2S source. In the mouse infection model, PEG-PALA nanoparticles encapsulated with ciprofloxacin (PEG-PALA@CIP) reduced the Salmonella colonization in the heart, liver, spleen, lung, cecum, and faeces, prolonged ciprofloxacin persistence in the intestine while reducing its absorption into the blood. More importantly, these nanoparticles reduced 3.4-fold of Enterobacteriaceae levels and increased 1.5-fold of the Lactobacillaceae levels compared with the drug administered in the free form. Moreover, these nanoparticles resulted in only minimal signs of intestinal tract inflammation. The H2S-responsive antibiotic delivery systems reported in this study demonstrating a variety of advantages including protected the drug from deactivation by gastric and intestinal fluids, maintained a high concentration in the intestinal tract and maximally kept the gut microbiota homeostasis. As such, this targeted antibiotic delivery systems are for the encapsulation of antibiotics to target specific enteropathogens.


Assuntos
Nanopartículas , Ácido Tióctico , Humanos , Camundongos , Animais , Ciprofloxacina/química , Células CACO-2 , Nanopartículas/química , Salmonella , Antibacterianos/química , Polietilenoglicóis/química , Sistemas de Liberação de Medicamentos , Mamíferos
3.
Angew Chem Int Ed Engl ; 60(8): 4289-4299, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33140558

RESUMO

Materials with multifunctionality or multiresponsiveness, especially polymers derived from green, renewable precursors, have recently attracted significant attention resulting from their technological impact. Nowadays, vegetable-oil-based waterborne polyurethanes (WPUs) are widely used in various fields, while strategies for simultaneous realization of their self-healing, reprocessing, shape memory as well as high mechanical properties are still highly anticipated. We report development of a multifunctional castor-oil-based waterborne polyurethane with high strength using controlled amounts of dithiodiphenylamine. The polymer networks possessed high tensile strength up to 38 MPa as well as excellent self-healing efficiency. Moreover, the WPU film exhibited a maximum recovery of 100 % of the original mechanical properties after reprocessing four times. The broad glass-transition temperature of the samples endowed the films with a versatile shape-memory effect, including a dual-to-quadruple shape-memory effect.

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