Surface charge-dependent effects of BSA-curcumin nanoparticles combined with amikacin in antimicrobial photodynamic therapy: A pilot In Vivo study of multidrug-resistant Pseudomonas aeruginosa skin infection

Abstract Skin infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa represent a significant therapeutic challenge because of high bacterial virulence and increasing antibiotic resistance. In this context, alternative strategies—such as nanotechnology and photodynamic therapy (PDT)—that can be combined with antibiotic therapy are being investigated as promising approaches for treating these infections. This study evaluated the therapeutic response of PDT mediated by anionic and cationic bovine serum albumin nanoparticles (NanoBSA) containing curcumin, in association with amikacin, in a murine model of cutaneous infection by MDR P. aeruginosa. The study was structured as a pilot trial involving 22 BALB/c mice infected and treated with free or nanoencapsulated curcumin and amikacin, followed by irradiation at 450 ± 10 nm. Blood and skin samples from the infected area were collected to analyze leukocyte profiles, serum inflammatory cytokines, and histopathological changes, and to measure changes in lesion area. The results demonstrated that the combination of PDT, NanoBSA, and amikacin promoted a greater reduction in lesion area, particularly with the anionic formulation. Leukocyte analysis indicated modulation of the inflammatory response, showing a more balanced profile in groups treated with amikacin, especially with the anionic formulation. Cytokine evaluation also showed modulation of the inflammatory response, most evident with the cationic formulation combined with amikacin. Histological findings showed improved tissue reorganization and structural preservation in groups undergoing combination therapy, with the anionic NanoBSA formulation standing out. Taken together, the results suggest that the combination of TFD, nanoencapsulated curcumin, and amikacin has therapeutic potential for treating cutaneous infections caused by MDR P. aeruginosa by promoting improved tissue repair and modulating the inflammatory response. Bacterial load was not quantified in the present study, which constitutes a limitation. Future studies should address this assay to confirm antimicrobial efficacy and help elucidate the underlying mechanisms.