Development of PLGA nanoparticles for siRNA delivery in cardiac cells

Abstract

Nanomaterials have emerged as alternatives to solve problems found in diverse areas, from metallurgical industry to medicine. In medicine, nanomaterials are widely used as drug delivery systems due to their advantages over traditional delivery platforms. In gene therapy, viral vectors are commonly used. However, viral vectors are related to immune responses, presenting safety concerns and hindering therapy effectiveness. The use of nanomaterials in gene therapy may overcome these obstacles, enhancing gene therapeutic effects. Gene therapy can be divided in two main approaches: gene overexpression or gene silencing. In gene silencing, it is common to use RNA interference (RNAi) techniques. Due to pathophysiological pathways elution, RNAi is proposed as a potential therapy against diseases such as cancer, and cardiovascular diseases (CVDs). CVDs are the leading causes of death worldwide. Currently cardiovascular therapies are not always effective, and the progress of CVDs inevitably leads to death. Therefore, there is an increasing interest in the development of novel cardiovascular therapies. For instance, RNAi technology is widely studied as a potential therapy against CVDs. However, RNAi effectors are labile molecules and can be easily degraded; therefore, a suitable vehicle for their delivery is essential. In this work, we study the use of PLGA, a polymer approved by FDA and EMA in diverse nanomaterial formulations, in the development of siRNA delivery systems. Our results demonstrate that PLGA nanoparticles of <150 nm, negative surface charge and high siRNA encapsulation efficiency, can be formulated. Moreover, in cardiac cells siRNA-loaded PLGA nanoparticles decrease MCU expression by 35.1 ± 2.7 % compared to non-loaded PLGA nanoparticles.