Nanocapsules to release the potential of antioxidants
A scientific study shows the potential of potent antioxidant encapsulation as a treatment against cardiovascular disease.
By Judith Bernal, Anay F. Lázaro, Gerardo García Rivas, and Omar Lozano
Dissemination Article
Antioxidants have captured great attention since the 1980s, following the formulation of the “French Paradox” hypothesis. The paradox refers to the observation that the French people have a reduced incidence of cardiovascular disease compared to other countries with similar caloric intake. The reason was eventually found to be consumption of red wine, which —regardless of its Dionysiac effects— is rich in antioxidants.
Antioxidants are thought to be suitable for use in the treatment of chronic and degenerative diseases associated with excessive levels of reactive oxygen species (ROS), as they can prevent cellular damage given both their ability to trap ROS and their potential to stimulate the cellular systems for ROS regulation. The use of these compounds may produce positive effects in patients afflicted by cardiovascular and neurodegenerative diseases, some types of cancer, type 2 diabetes, and aging.
Studies in cells have extensively shown the benefits of using antioxidant compounds to reduce excessive ROS levels, which leads to the maintenance of the cellular state. However, preclinical and clinical studies have yielded limited results. This is because antioxidants exhibit low bioavailability due to their physicochemical properties and high rate of metabolization.
The experiment
As we looked for ways to release the potential of these compounds, we found that nanocapsule transport could help overcome the abovementioned hurdles. The research paper titled “Nanoencapsulated Quercetin Improves Cardioprotection during Hypoxia-Reoxygenation Injury through Preservation of Mitochondrial Function” reports the findings from the first phase of a research project testing encapsulation of potent antioxidant quercetin as a potential treatment against cardiovascular disease.
The objective of this study was to determine quercetin delivery capability by using quercetin polymeric nanocapsules or unencapsulated, free quercetin. To achieve this goal, we utilized an in vitro model of cardiac cells. We first sought to characterize encapsulated quercetin. Nanoparticles with an average diameter of 165 ± 7.5 nm (a million times less than the diameter of a human hair) were obtained and a 98% encapsulation efficiency was achieved for quercetin in the particles. Within the simulated cell interior, quercetin release from the nanocapsules reached more than 90% after two weeks, confirming sustained substance release.
The study also showed that poly(lactic-co-glycolic) acid (PLGA) nanocapsules can penetrate H9c2 cardiac cells after incubation for 24 hours.
The next natural step in a study with encapsulated antioxidants was to evaluate nanocapsule ability to deal with a sudden increase in ROS levels, which was induced by using a compound known as antimycin A (AA). Under these conditions, encapsulated quercetin was found to reduce ROS levels within the cytosol (inside of the cell) by 52% compared to 8% of free quercetin. These data demonstrate the effectiveness of nanoencapsulation as a delivery strategy.
Finally, H9c2 cardiac cells were subjected to a hypoxia/reoxygenation process aimed at reproducing some of the adverse conditions observed during an acute myocardial infarction. This model is useful as a proof-of-concept for the potential principles of cardioprotection. Our results indicate that percent cell survival with encapsulated quercetin and free quercetin was 77% and 67%, respectively. Based on these results, we decided to analyze mitochondrial function, as dysfunction of this key cell organelle irremediably leads to cell death. Treatment with nanocapsules was found to be better at protecting mitochondria in terms of oxygen consumption capacity and maintenance of membrane potential, essential elements for energy production.
The findings
By using a cardiac cell model subjected to simulated heart ischemia/reperfusion conditions, this study showed that treatment with encapsulated quercetin leads to higher cell survival rates associated with mitochondrial protection. Why does encapsulated quercetin offer better protection than free quercetin? We found the answer in the stability levels of the original compound: while encapsulated quercetin exhibits a similar light absorbance pattern at any time scale (up to two weeks), during stability simulations under cellular medium conditions, free quercetin exhibited a change in absorbance pattern associated with compound oxidation. We thus showed that polymeric nanocapsules protect quercetin against degradation.
What are the implications of this study? The first phase of this research project confirmed the success of a novel strategy for the treatment of ROS-mediated diseases using an encapsulated antioxidant, which remained protected from degradation within a delivery system that allows for controlled, sustained substance release. Based on these findings, it seems appropriate to continue exploring the strategy in in vivo models and, if the premise still holds true, in clinical studies to find ways to release the potential of antioxidant agents.
About the authors
Judith Bernal Ramírez holds a master’s degree in biotechnology from Tec de Monterrey. She is currently pursuing a Ph.D. degree in biotechnology at the Tec de Monterrey School of Engineering and Science (Monterrey campus). judithbernal.rmz@tec.mx
Anay F. Lázaro Alfaro holds a master’s degree in biotechnology from Tec de Monterrey. She belongs to the Cardiovascular Medicine and Metabolomics Research Group. a.lazaro@tec.mx
Gerardo García Rivas holds a Ph.D. degree in biomedical sciences. He is a research professor at the Tec de Monterrey School of Medicine and Life Sciences and leader of the Cardiovascular Medicine and Metabolomics Research Group. He is also a member of the National System of Researchers (level 2). gdejesus@tec.mx
Omar Lozano García holds a Ph.D. degree in physics. He is a research professor at the Tec de Monterrey School of Medicine and Life Sciences. He belongs to the Cardiovascular Medicine and Metabolomics Research Group. He is also a member of the National System of Researchers (level 1). omar.lozano@tec.mx
Do you want to learn more?
The research paper Nanoencapsulated Quercetin Improves Cardioprotection during Hypoxia-Reoxygenation Injury through Preservation of Mitochondrial Function, recently indexed in the Scopus database, can be found at https://doi.org/10.1155/2019/7683051
