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Publication
Targeting liver ischemia and reperfusion injury: nanoformulations for advanced drug/gene delivery
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Abstract(s)
Hepatic ischemia and reperfusion injury (IRI) is an acute inflammatory process that may result from surgical interventions, such as liver resection or transplantation. This pathology has become a severe clinical issue, due to the increased incidence of hepatic cancer and the high number of liver transplants. So far, effective treatments have not been implemented, being crucial the development of new approaches. Drug delivery nanosystems have proved to be a major asset in therapy because of their ability to optimize drug delivery.
In this work, distinct nanosystems were proposed to tackle the disadvantages of the existent treatments: anti-inflammatory-loaded long-circulating liposomes (ibuprofen, indomethacin or quercetin) or gold nanoparticles functionalized with poly(ethylene glycol) (PEG) and antisense oligonucleotides specific for silencing human TNFA gene (AuNPs_TNF-α) associated or not with liposomes. All nanosystems were characterized in terms of their physicochemical properties and stability.
The in vitro therapeutic effect of quercetin liposomes was assessed in a hypoxia chamber model, where a decrease in pro-inflammatory biomarkers expression was observed. Using an in vivo hepatic IRI model, quercetin liposomes showed an anti-inflammatory effect and promoted hepatic lesions recovery.
The association of AuNPs_TNF-α with liposomes was successfully accomplished but distinct methodologies were required to enhance their association. The in vitro anti-inflammatory effect of free and liposomal AuNPs_TNF-α was evaluated. When inflamed cells were treated with 25 nM of ASO using liposomal AuNPs_TNF-α, no silencing effect was observed and a 11-15% reduction in cellular viability was obtained. When an ASO concentration of 240 nM was used, 4 h or 6 h incubation with free AuNPs_TNF-α resulted in a decrease in TNF-α mRNA expression of 18% and 59%, respectively, without cytotoxic effects.
In conclusion, the results suggested that quercetin liposomes and AuNPs_TNF-α might be potential therapeutic strategies to improve hepatic IRI treatment, overcoming the drawbacks presented by currently used therapies.
Description
Keywords
lesão induzida por isquémia e reperfusão hepática lipossomas nanopartículas de ouro quercetina oligonucleótidos antisense hepatic ischemia and reperfusion injury liposomes gold nanoparticles quercetin antisense oligonucleotides