Nanostructured systems based on pluronics to carry gold nanoparticles and methylene blue aiming for multimodal therapy

Abstract

The rise of multidrug-resistant microorganisms has become a cause of concern in the biomedical field. In this sense, this study focuses on the development of an effective treatment for infectious diseases mediated by Multimodal Therapy, combining Photodynamic Therapy (PDT), and Photothermal Therapy (PTT). The system involves the synthesis and stabilization of gold nanoparticles (AuNPs) in Pluronic® micelles of F-127 and P-84, combined with the Methylene Blue (MB) aiming effects against microorganisms. It is noteworthy that the AuNPs were synthesized in situ in the copolymer using the solid dispersion technique. These copolymers were strategically chosen for evaluation purposes with our study involving P-123 previously published in this journal. Thus, the effect of the length of the PEO and PPO blocks can be delineated concerning the synthesis of AuNPs. In this case, copolymer F127 has PPO blocks identical to P-123 while P-84 has PEO blocks compatible with P-123. Characterization of the formulations included electronic absorption spectroscopy, dynamic light scattering, and transmission electron microscopy. Fluorescence quenching studies by Stern Volmer plots indicated the location of the MB in the hydrophilic corona of the micelles. In general, was verified that reducing the PEO/PPO ratio favors the formation of AuNPs, possibly due to the greater number of reducing sites per unit mass of the polymer. The formulations remained stable for at least 15 days, and photothermal studies showed a temperature increase of at least 11 °C. The photothermal effect proved reversible after three heating–cooling cycles, revealing a synergy between MB and AuNPs in heat generation, hindered by increased irradiance and rapid photobleaching of MB. The in vitro susceptibility tests with Candida albicans and Staphylococcus aureus demonstrated effective inhibition of the microorganisms. The result shows that AuNPs for itself do not affect the fungal/bacteria lineage. However, the MB/AuNPs combination samples, showed excellent fungal and bacterial inhibition at low drug concentrations.