Developing a new polymeric system for release of immunomodulators for treatment of heart failure

Abstract

During recent years the role of the immune system in the progression of heart failure (HF) has become an area of interest to better understand the physiopathological mechanisms of its progression. Some immunomodulators have been tested for efficacy in reducing inflammatory mediators in patients with HF. However, one of the greatest limitations encountered when trying to bring those treatments to patients is the side effect of these drugs. Keeping this in mind, nanotechnology has been advancing rapidly during the past few years. Nanoparticles can carry medications and have active tissue targeting properties, and such characteristics could increase the drug tolerance, which are known to have a narrow therapeutic window. Using this knowledge we used a well‐known immunomodulator, either free or encapsulated in a polymeric nanoparticle to treat a murine model of HF by inducing an anti‐inflammatory effect, and thus, reduce the progression ventricular dysfuction.MethodsThe immunomodulator was encapsulated in a polymeric nanoparticle by an oil‐in‐water emulsion. The resulting nanovector was analyzed in terms of size, surface charge, drug loading and release profile.ResultsThe nanovector was of ~ 100 nm in size, −30 mV in surface charge, 95 % entrapment efficiency, and a release profile consistent with reported data. Mice model of HF shown fibrosis and cardiac remodeling, however this damage was reduced in the animals that received the immunomodulator (1 mg/Kg week). Likewise, a 4‐fold increase in the production of IL‐10 was observed. Moreover, the use of polymeric nanoparticles required a lower dose to reach a similar cardioprotective effect.Support or Funding InformationSupported by ITESM and CONACyTThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.