Self-assembled Amino acid based copolymer Nanoparticles for Wound Healing and tissue regeneration: structure studied through Molecular Dynamic Simulation

Abstract

Amino acid-based block copolymer nanoparticles with cross-linkers have garnered growing interest in recent years. However, its’ intricate synthesis and purification difficulties, along with stability concerns linked to intermicellar crosslinking, restrict their potential use in healthcare and therapeutic applications. In this line, the present work is aimed to design amphiphilic block copolymer nanoparticles of N-acryloyl glycine and N-acryloyl-(L-phenylalanine methyl ester), i.e., p(NAG-co-NAPA)wc, without using a cross-linker via miniemulsion free radical polymerization. The self-assembled π-π stacking structural arrangement of copolymer at different temperatures has been confirmed through the molecular dynamics (MD) simulation, which corroborated the structural stability of copolymer nanoparticles at physiological temperature (37oC). The cell migration results of p(NAG-co-NAPA)wc nanoparticles are complementary to the CEMA assay and reveal their tissue regeneration properties. Further, the in vivo wound healing study demonstrated that within 13 days of post-treatment, the wound can be healed ~97%, whereas for the control, it is found to be only ~80%. Additionally, the RT-PCR results revealed that p(NAG-co-NAPA)wc nanoparticles possess anti-inflammatory and tissue regeneration properties by downregulating TNF-α and IL-1β; and upregulating PECAM-1 and VEGF-A, respectively. In conclusion, this p(NAG-co-NAPA)wc nanoparticles are paramount with an extensive clinical potential for the regeneration of acute wounds and can be used for other therapeutic applications.