Novel Nanophotosensitizers Employing Poly(Acrylamide‐Co‐ N ‐Isopropylacrylamide) Nanoparticles for Antimicrobial Photodynamic Therapy

Various specially designed poly(acrylamide-co-N-isopropylacrylamide) (PAA-NIPA) nanoparticles (NPs) with different acrylamide (AA)/NIPA molar compositions were synthesized by microemulsion polymerization and evaluated as carriers for photosensitizers (PSs) for antimicrobial photodynamic therapy (aPDT). In the search for ideal PS, this work was based on improving some properties and treatment efficiency of phenazine and phenothiazine compounds, more specifically on the halogenated derivatives Neutral Red (NRBr) and Azure B (AzBBr). These second-generation PSs were found to have promising properties as antimicrobial agents. However, they presented some undesirable properties, such as low solubility, aggregation, and chemical instability, which could be overcome by using drug delivery systems, giving rise to third-generation PSs. The five new NPs presented adequate size and dispersibility for pharmaceutical uses. Furthermore, these NPs allowed the vehiculization of NRBr and AzBBr. The new third-generation PSs have demonstrated better photochemical reactivity and chemical stability than free PSs. The improved physicochemical and photophysical properties of these nanophotosensitizers were accompanied by a significant increase in the photoantimicrobial action of Gram-positive and Gram-negative bacteria. Therefore, the use of this vehicle strategy has improved the properties of NRBr and AzBBr and converts these systems into major applicants for their application in aPDT.