Switchable adhesive films of pullulan loaded with a deep eutectic solvent-curcumin formulation for the photodynamic treatment of drug-resistant skin infections

Sónia N Pedro; Bruno F A Valente; Carla Vilela; Helena Oliveira; Adelaide Almeida; Mara G Freire; Armando J D Silvestre; Carmen S R Freire

doi:10.1016/j.mtbio.2023.100733

Switchable adhesive films of pullulan loaded with a deep eutectic solvent-curcumin formulation for the photodynamic treatment of drug-resistant skin infections

Mater Today Bio. 2023 Jul 14:22:100733. doi: 10.1016/j.mtbio.2023.100733. eCollection 2023 Oct.

Authors

Sónia N Pedro¹, Bruno F A Valente¹, Carla Vilela¹, Helena Oliveira², Adelaide Almeida², Mara G Freire¹, Armando J D Silvestre¹, Carmen S R Freire¹

Affiliations

¹ CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.
² CESAM, Department of Biology, University of Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.

Abstract

Antimicrobial photodynamic therapy (aPDT) is a potent tool to surpass the global rise of antimicrobial resistance; still, the effective topical administration of photosensitizers remains a challenge. Biopolymer-based adhesive films can safely extend the residence time of photosensitizers. However, their wide application is narrowed by their limited water absorption capacity and gel strength. In this study, pullulan-based films with a switchable character (from a solid film to an adhesive hydrogel) were developed. This was accomplished by the incorporation of a betaine-based deep eutectic solvent (DES) containing curcumin (4.4 μg.cm^-2) into the pullulan films, which tuned the films' skin moisture absorption ability, and therefore they switch into an adhesive hydrogel capable of delivering the photosensitizer. The obtained transparent films presented higher extensibility (elongation at break up to 338.2%) than the pullulan counterparts (6.08%), when stored at 54% of relative humidity, and the corresponding hydrogels a 4-fold higher adhesiveness than commercial hydrogels. These non-cytotoxic adhesives allowed the inactivation (∼5 log reduction), down to the detection limit of the method, of multiresistant strains of Staphylococcus aureus in ex vivo skin samples. Overall, these materials are promising for aPDT in the treatment of resistant skin infections, while being easily removed from the skin.

Keywords: Adhesive films; Bacterial resistance; Curcumin; Deep eutectic solvents; Photodynamic therapy; Pullulan; Skin infections; Switchable behavior.