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1.
Mater Today Bio ; 28: 101181, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39221217

RESUMO

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

2.
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
3.
Nutrients ; 16(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38337666

RESUMO

Prebiotics and postbiotics have gained attention as functional food additives due to their substantial influence on the gut microbiome and potential implications for human health on a broader scale. In addition, the number of patents for these additives has also increased, yet their functional classification has been problematic. In this study, we classified 2215 patents granted from 2001 to 2020 by functionality to enable predictions of future development directions. These patents encompassed subjects as diverse as feed supplementation, regulation of intestinal homeostasis, prevention of gastrointestinal ailments, targeted drug administration and augmentation of drug potency. The progression of patents issued during this time frame could be divided into three phases: occasional accounts prior to 2001, a period from 2001 to 2013 during which an average of 42 patents were issued annually, followed by a surge exceeding 140 patents annually after 2013. The latter increase has indicated that pre- and post-biotics have been recognized as biologically relevant. Patent mining therefore can enable forecasts of the future trajectory of these biologics and provide insights to evaluate their advancement. Moreover, this research is the first attempt to generalize and predict the directions of prebiotics and postbiotics using patent information and offers a comprehensive perspective for the potential utilization of prebiotics and postbiotics across a wide variety of fields.


Assuntos
Microbioma Gastrointestinal , Probióticos , Humanos , Prebióticos , Intestinos
4.
J Nanobiotechnology ; 21(1): 483, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104180

RESUMO

Salmonellosis is a globally extensive food-borne disease, which threatens public health and results in huge economic losses in the world annually. The rising prevalence of antibiotic resistance in Salmonella poses a significant global concern, emphasizing an imperative to identify novel therapeutic agents or methodologies to effectively combat this predicament. In this study, self-assembly hydrogen sulfide (H2S)-responsive nanoprodrugs were fabricated with poly(α-lipoic acid)-polyethylene glycol grafted rhein and geraniol (PPRG), self-assembled into core-shell nanoparticles via electrostatic, hydrophilic and hydrophobic interactions, with hydrophilic exterior and hydrophobic interior. The rhein and geraniol are released from self-assembly nanoprodrugs PPRG in response to Salmonella infection, which is known to produce hydrogen sulfide (H2S). PPRG demonstrated stronger antibacterial activity against Salmonella compared with rhein or geraniol alone in vitro and in vivo. Additionally, PPRG was also able to suppress the inflammation and modulate gut microbiota homeostasis. In conclusion, the as-prepared self-assembly nanoprodrug sheds new light on the design of natural product active ingredients and provides new ideas for exploring targeted therapies for specific Enteropathogens. Graphical  illustration for construction of self-assembly nanoprodrugs PPRG and its antibacterial and anti-inflammatory activities on experimental Salmonella infection in mice.


Assuntos
Sulfeto de Hidrogênio , Infecções por Salmonella , Animais , Camundongos , Salmonella typhimurium , Sulfeto de Hidrogênio/química , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Antibacterianos/farmacologia
5.
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
6.
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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