Abstract
Ischemia and reperfusion injury (IRI) is a common complication caused by inflammation and oxidative stress resulting from liver surgery. Current therapeutic strategies do not present the desirable efficacy, and severe side effects can occur. To overcome these drawbacks, new therapeutic alternatives are necessary. Drug delivery nanosystems have been explored due to their capacity to improve the therapeutic index of conventional drugs. Within nanocarriers, liposomes are one of the most successful, with several formulations currently in the market. As improved therapeutic outcomes have been demonstrated by using liposomes as drug carriers, this nanosystem was used to deliver quercetin, a flavonoid with anti-inflammatory and antioxidant properties, in hepatic IRI treatment. In the present work, a stable quercetin liposomal formulation was developed and characterized. Additionally, an in vitro model of ischemia and reperfusion was developed with a hypoxia chamber, where the anti-inflammatory potential of liposomal quercetin was evaluated, revealing the downregulation of pro-inflammatory markers. The anti-inflammatory effect of quercetin liposomes was also assessed in vivo in a rat model of hepatic IRI, in which a decrease in inflammation markers and enhanced recovery were observed. These results demonstrate that quercetin liposomes may provide a significant tool for addressing the current bottlenecks in hepatic IRI treatment.
Highlights
Was dissolved in methanol (HPLC gradient grade, Merck, Darmstadt, Germany), and this solution was added to the lipid components (cholesterol (Chol—Merck, Darmstadt, Germany), soybean L-α-phosphatidylcholine (SPC—Lipoid S100, Lipoid GmbH, Ludwigshafen, Germany), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-2000] (DSPE-mPEG2000 —Lipoid GmbH, Germany)) that were dissolved in chloroform (≥99.9%, Merck, Germany) and evaporated until dry in a rotatory evaporator (Buchi Rotavapor RE-111, Lugo, Switzerland), forming a lipid film
8 ofof 261:10 was selected since the incorporation efficiency obtained was around 100%, being superior to the values reported in literature [19,20,21]
The developed in vivo rodent model presents characteristics in accordance with the reported features of hepatic Ischemia and reperfusion injury (IRI)—namely, high levels of serum transaminases activity, elevated levels of mRNA TNF-α expression, and histological alterations [55,56,57]
Summary
Pharmaceutics 2022, 14, 104 stress and inflammation [2,3]. The use of drug delivery nanosystems (DDS), known to enhance the therapeutic index, reduce the required drug load, and minimize adverse side effects [5,6,7], could be beneficial in overcoming the hindrances presented by current IRI treatments. In this context, liposomes are one of the most promising nanocarriers, with several formulations approved for clinical use [8]. In addition to the possibility of tailoring the characteristics of liposomal formulations according to the desired purpose (e.g., to cross biological barriers or accumulate in specific sites), they offer other advantages including biocompatibility, biodegradability, low toxicity, capacity to transport large quantities of therapeutic agents, and ability to self-assemble [9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
