HYDROGELS MEET LIGHT IN ENGINEERING PHOTOACTIVE SYSTEMS FOR TOPICAL PHOTODYNAMIC APPLICATIONS

Antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative

against topical infections, but its effectiveness is often limited by poor retention and

rapid dispersion of photosensitizers (PSs) at the site of infection. In this study, hybrid

thermosensitive hydrogels were developed based on poloxamer (Pluronic® F127,

20% w/v) and incorporating the phenothiazinium PS 1,9-dimethylmethylene blue

(DMMB, 30 μM). To modulate physicochemical and mechanical properties, additional

polymers were incorporated at 0.5% (w/v), including hydroxypropyl methylcellulose

(HPMC 10 and HPMC 90), hydroxyethyl cellulose (HEC 90), alginate (AG), and

xanthan gum (XG). The formulations exhibited suitable pH values (5-6) and preserved

the characteristic absorption profile of DMMB over 30 days, indicating high

photochemical stability. Rheological analysis revealed predominantly elastic behavior 

photochemical stability. Rheological analysis revealed predominantly elastic behavior

-thinning properties, favorable for topical application and in situ

gelation. Scanning electron microscopy revealed dense, interconnected

microstructures, while FTIR analysis confirmed that interactions between components

were primarily physical, driven by hydrogen bonding rather than chemical modification.

Photodynamic assays against Candida auris demonstrated a pronounced lightdependent

antifungal effect. Control groups (light alone and dark conditions) showed

no significant reduction in fungal growth, confirming the specificity of aPDT. Upon

irradiation (662 ± 15 nm, 30 J/cm²), all DMMB-loaded hydrogels promoted a timedependent

decrease in fungal viability, with near-complete inhibition after prolonged

exposure. Cellulose-based formulations (HPMC and HEC) showed superior antifungal

performance, whereas alginate- and xanthan-based systems exhibited reduced

efficacy, likely due to differences in matrix organization affecting PS diffusion and

availability. Overall, these findings demonstrate that DMMB-loaded thermosensitive

hydrogels (PL 20% w/v + polymers 0.5% w/v) represent a promising strategy for

enhancing topical aPDT, providing improved retention, controlled release, and

effective antifungal activity against Candida auris.

This work was supported by Conselho Nac. Des. Cient. Tecnológico (CNPq, Universal

# 420645/2023-3) and by São Paulo Research Foundation (FAPESP # 2021/14119-

6).