Hydrogel releasing drug as a new alternative to treat complications of a heart attack

3.-Spheres-entering-bloodstreamReports about effectiveness of stem cells therapy after an episode of acute coronary syndrome have been appearing for a long time. Interesting aspects of this kind of treatment are time of therapy implementation, dose, mechanism leading to improvement of the heart muscle functioning and method of administration. A method described by German research team seems to be a solution to the last problem. It was published in May this year and consists in the use of biomaterial – hydrogel made of PEGda which releases bispecific protein influencing bone marrow stem cells in a chemotactical way.

According to WHO data, ischemic heart disease (IHD) was the most frequent cause of deaths over the world in 2012 (7.4 m). Sequence of events in the heart muscle after ischemic episode leads to the development of a scar and impairment of heart function as a pomp. Regarding increasing incidence of IHD, the need for new and effective treatment methods is becoming higher.

Improvement of heart functions was observed in animal models which after acute coronary syndrome were treated with the use of stem cells. It resulted from paracrine cytokines secretion, vascular endothelial growth factor (VEGF) and is obtained by neovascularisation and reduction of heart attack area. One of such cytokines is SDF1 (stromal cell-derived factor 1) which binds through CXCR4 receptor to endothelial progenitor cells which have a key role in development of new vessels.

The aim of German research team was to devise biomaterial which would constantly release medicine. Such features are found in hydrogel made of polyethylene glycol diacrylate PEGda which binds bispecific SDF1-GPVI protein (devised by Ziegler et.al). GPVI domain binds to collagen of the extracellular matrix which is exposed in blood vessels after damage of wall as a result of atherosclerotic plaque rupture. Therefore, collagen serves as a place to fix the drug and makes possible to place it precisely in heart attack area. What is more, it ensures sufficiently high chemokine concentration which is necessary to attract EPC cells. Effectiveness of such drug was proved in research on mice. After direct injection of the medicine CXCR4+ cells appeared in heart attack area already after 5 days but they remained for no longer than 28 days. Therefore, it is predicted that long lasting release of such protein would bring more benefits in improvement of heart function after a heart attack.

In this research scientists precisely devised production of PEGda hydrogel networked under the influence of UV (365nm wavelength and 5mW/cm2 irradiance). It in vitro releases a drug which has properties similar to medicine administered in injections. Additional benefit of hydrogel is possibility not only to adjust amount of released drug by precise control of protein dose used to its production, but also crosslinking degree.

Concept of using PEGda hydrogel releasing SDF1-GPVI is an attractive method to improve systolic heart function after a heart attack. However, the method needs confirmation of in vitro research.

Written by: Izabella Drogoń, Irmina Kmieć, Jakub Patryn, Jerzy Bednarski

Source:
1. Preserved bioactivity and tunable release of a SDF1-GPVI bi-specific protein using photo-crosslinked PEGda hydrogels. Biomaterials: Marianne K. Schesny, Michael Monaghan, Andrea H. Bindermann, Désirée Freund, Martina Seifert, Johannes A. Eble, Sebastian Vogel, Meinrad P. Gawaz, Svenja Hinderer, Katja Schenke-Layland (2014)
2. The Bispecific SDF1-GPVI Fusion Protein Preserves Myocardial Function After Transient Ischemia in Mice. Circulation: Melanie Ziegler, Margitta Elvers, Yvonne Baumer, Christoph Leder, Carmen Ochmann, Tanja Schönberger, Tobias Jürgens, Tobias Geisler, Burkhard Schlosshauer, Oleg Lunov, Stefan Engelhardt, Thomas Simmet, Meinrad Gawaz (2012)
3. http://who.int/mediacentre/factsheets/fs310/en/

Would You like to know more? Watch on MEDtube.net: Heart Ischemia

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