Fishroesomes show intrinsic anti-inflammatory bioactivity and ability as celecoxib carriers in vivo.

Abstract

According to the World Health Organization (WHO), chronic inflammatory-related diseases represent the greatest threat to human health. Indeed, failure in the resolution of inflammation leads to serious pathological conditions, such as cardiovascular diseases, arthritis, cancer, diabetes, autoimmune diseases, and neurodegenerative disorders that are often associated with extremely high human suffering and societal and economic burdens. Despite the number and efficacy of available therapeutic agents have been increased, the serious side effects associated with some of them often create a very high risk/benefit ratio for patients. Therefore, herein, a drug delivery system was engineered to overcome important drawbacks of conventional therapies and to have a synergistic action with the incorporated drug. Indeed, it will have an added beneficial role in controlling inflammation. For that, sardine (Sardina pilchardus) roe was used as the lipidic source to produce bioactive liposomes, namely fishroesomes. These spherical vesicles with ≈326 nm in size and a significant negative surface charge (≈-31 mV) were able to encapsulate and control the release of the anti-inflammatory drug celecoxib. Moreover, fishroesomes were cytocompatible for different cell types (chondrocytes and macrophages), at concentrations in which they present anti-inflammatory properties. Importantly, fishroesomes were more effective in reducing pro-inflammatory mediators than the free drug. We also demonstrated that a single intra-articular injection of the fishroesomes encapsulating or not celecoxib in an experimental rat model of inflammatory arthritis was safe and more effective in controlling the pain and reducing the synovial inflammation compared to the free drug. Notably, as the celecoxib concentration in the sardine roe-derived liposomes was less than half of the amount of free drug, this study demonstrates the value of fishroesomes in counteracting inflammation. Therefore, the developed formulations may be considered a promising therapeutic option for inflammatory conditions.