Fabrication of co-polymeric nanoformulation loaded with antibiotic ofloxacin and immunosuppressant tacrolimus for pediatric sepsis-induced acute lung injury

Abstract

Sepsis is a complicated, life-threatening illness caused by pathogen invasion triggered by a dysfunctional immune system in the host. Even though several antimicrobial and immunosuppressive therapies have been suggested, no clinically viable treatments for sepsis exist. This research aims to find a way to cure sepsis and reduce its symptoms by creating a nanoparticle system that specifically targets inflammation and drug delivery sites. To fabricate the PLGA-NPs loaded with the wide-range antibiotic Ofloxacin (OFX) and the immunosuppressant anti-inflammatory Tacrolimus (TCR), we opted for the biocompatible and biodegradable PLGA (poly(lactide-co-glycolide acid)). Grafting the γ3 peptides that can selectively conjugate to the intercellular adhesion molecule-1 (ICAM-1), which is abundantly articulated on the inflammatory endothelium cells surface, confers the targeting capacity of the nanoparticles toward inflammatory areas. Good biocompatibility, lower hemolytic rate, and minimal toxicity are hallmarks of dual drug-loaded γ3@PLGA nanoparticles. This work presents a straightforward and sturdy nanoplatform for treating pediatric sepsis-induced acute lung injury as a first step toward developing multifunctional nanomedicine for clinical translation.