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1.
Ann Biomed Eng ; 45(4): 1058-1068, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27761766

RESUMO

The human gastrointestinal tract is the primary site of colonization of multidrug resistant pathogens and the major source of life-threatening complications in critically ill and immunocompromised patients. Eradication measures using antibiotics carry further risk of antibiotic resistance. Furthermore, antibiotic treatment can adversely shift the intestinal microbiome toward domination by resistant pathogens. Therefore, approaches directed to prevent replacement of health promoting microbiota with resistant pathogens should be developed. The use of non-microbicidal drugs to create microenvironmental conditions that suppress virulence of pathogens is an attractive strategy to minimize the negative consequences of intestinal microbiome disruption. We have previously shown that phosphate is depleted in the intestinal tract following surgical injury, that this depletion is a major "cue" that triggers bacterial virulence, and that the maintenance of phosphate abundance prevents virulence expression. However, the use of inorganic phosphate may not be a suitable agent to deliver to the site of the host-pathogen interaction since it is readily adsorbed in small intestine. Here we propose a novel drug delivery approach that exploits the use of nanoparticles that allow for prolonged release of phosphates. We have synthesized phosphate (Pi) and polyphosphate (PPi) crosslinked poly (ethylene) glycol (PEG) hydrogel nanoparticles (NP-Pi and NP-PPi, respectively) that result in sustained delivery of Pi and PPi. NP-PPi demonstrated more prolonged release of PPi as compared to the release of Pi from NP-Pi. In vitro studies indicate that free PPi as well NP-PPi are effective compounds for suppressing pyoverdin and pyocyanin production, two global virulence systems of virulence of P. aeruginosa. These studies suggest that sustained release of polyphosphate from NP-PPi can be exploited as a target for virulence suppression of lethal pathogenic phenotypes in the gastrointestinal tract.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Enteropatias , Nanopartículas/química , Oligopeptídeos/biossíntese , Polietilenoglicóis , Polifosfatos , Pseudomonas aeruginosa/metabolismo , Piocianina/biossíntese , Fatores de Virulência/biossíntese , Hidrogéis/química , Hidrogéis/farmacologia , Enteropatias/tratamento farmacológico , Enteropatias/metabolismo , Enteropatias/microbiologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polifosfatos/química , Polifosfatos/farmacologia , Pseudomonas aeruginosa/patogenicidade
2.
ACS Appl Mater Interfaces ; 4(3): 1397-403, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22304468

RESUMO

Herein, we report a simple method to fabricate patterned organic/inorganic hybrid 1DPCs by top-down assisted photolithography. Versatile colorful pattern with different size and shape can be produced by selectively exposing the 1DPCs under UV light with predesigned photomask directly. The period change, especially the thickness variation of the top polymer layer, is the main reason for the colorful pattern generation. Because of the swelling property of the polymer layers, the pattern color can be modulated by introducing or taking off organic solvents, leading the as-prepared patterned 1DPCs to be effective sensors with high selectivity.

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