A novel neutral red derivative loaded into polymeric nanoparticles: study of its photoinactivation against Staphylococcus aureus

Abstract

We report the synthesis, characterization, and evaluation of the physicochemical and antimicrobial properties of a new derivative of neutral red named neutral red acid (NRAc). Relevant pharmaceutical and photochemical parameters – including pK_a, stability, photostability, and reactive oxygen species (ROS) generation – were assessed. Additionally, NRAc was loaded into polyacrylamide nanoparticles (PAA-NPs), and its biological activity was evaluated. The compound was synthesized via a rapid, straightforward method without requiring purification, achieving a relative purity of 93%. Compared to the parent molecule, NRAc exhibited enhanced physicochemical properties and showed promising biocompatibility; at a concentration of 40 µM, it caused no hemolysis after 15 min of light exposure, and less than 1% after 30 min. Although it displayed limited solubility in aqueous media, encapsulation in PAA-NPs enabled effective antimicrobial performance. The nanoparticle-loaded photosensitizer significantly reduced the survival of methicillin-resistant Staphylococcus aureus (MRSA) to below 10% following photodynamic treatment. These results highlight the potential of this novel compound as a promising third-generation photosensitizer for application in antimicrobial photodynamic therapy (aPDT).