Poly(N-acryloyl-L-phenylalanine) nanoparticles for potential treatment of inflammation for selective Organs

Abstract

Systemic inflammation can lead to multi-organ failure. The existing anti-inflammatory components possess adverse side effects and the present situation demands new medicine with high therapeutic efficiency. Polymeric nanoparticles based on amino acids could be one of the best alternative solution due to their cytocompatibility and immune responses. Herein, we have synthesized polymeric nanoparticles (Phe NPs) of size 20-30 nm using N-Acryloyl-L-phenylalanine methyl ester as a precursor. The biological and immune response of Phe NPs is found to be commanding, which has been proven by using immune cells (RAW 264.7 macrophages). In vitro study revealed that these NPs can easily be uptaken (~98%) by the immune cells and reduce the inflammation by improving the immune response. In silico molecular docking results revealed that the Phe NPs could potentially interact with immune cytokines such as IL-6, NF-κβ, TNF-α, COX2 and IL-1β. Phe NPs exhibit a similar type of binding and interaction as ibuprofen (IBF), which is a strong evidence towards its immune property to control the inflammation. Anti-inflammatory response of Phe NPs has been established through the in vitro inflammation model developed in LPS-stimulated RAW 264.7 macrophages. Further, an LPS-induced in vivo rat model was developed and the study revealed that Phe NPs are useful for the treatment of systemic inflammation. The blood-based biochemical parameters, such as C-reactive protein, Lactate and procalcitonin were checked and the anti-inflammation responses of Phe NPs confirmed through the RT-PCR analysis by measuring the levels of inflammatory markers such as TNF-α, IL-6 and VEGF. Finally, in vivo systemic inflammation rat model was used to check on the systemic organs (brain, liver, kidney, spleen, lung and heart) before and after the treatment by Phe NPs to prove it’s anti-inflammatory responses. H&E histological analysis of different organs further revealed that Phe NPs even at low doss of 100µg kg-1 is immune responsive/protective and anti-inflammatory in nature.