Hydrogel incorporating Nanocomplexes based on Captisol® and a Cationic Porphyrin for Wound Infection Treatment

Microbial control strategies in wound treatment are currently being developed to effectively inactivate pathogens, overcoming multidrug resistance (MDR). As part of our ongoing research into phototherapy and photodiagnostics, we have focused on designing “smart” supramolecular systems entrapping nanophotosensitizers1,2 (nanoPS). Here we present the development of rapidly resorbable hydrogels based on DAC® (a hyaluronic acid grafted with polylactic acid polymer, HA-PLA) incorporating a nanoPS made of a cyclodextrin (CD)/photosensitizer system to control wound infections. In particular, the nanocarrier CAPTISOL® (sulfobutyl ether-beta-cyclodextrin) which entraps the cationic porphyrin (N-methyl-4-pyridyl)-21H,23Hporphyrin (TMPyP)), protects the porphyrin from photodegradation, thus to increase its efficacy in antimicrobial photodynamic therapy (aPDT). CAPTISOL®/TMPyP complex was prepared by mixing the two precursors in ultrapure water at 5:1 CD/PS molar ratio, the complex was then freeze-dried, resuspended in water and mixed with DAC® powder to get CAPTISOL®/TMPyP -loaded DAC®. In order to investigate the effects of the hydrogel upon local application in wound infection, CAPTISOL®/TMPyP -loaded DAC® was diluted to 0.3 % v/w and a nanohydrogel was obtained and characterized as erosion product in infected site. The interaction of neat TMPyP and in presence of cyclodextrin within the hydrogel was studied using various spectroscopic techniques, including UV/Vis absorption, steady-state and timeresolved fluorescence, and Dynamic Light Scattering (DLS). Nanohydrogel showed photobactericidal activity against Gram-positive and Gram-negative bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, vancomycin-resistant Enterococcus faecium (VREfm) DSM 17050 and VIM-2-producing Pseudomonas aeruginosa DSM102273. In vitro photoantimicrobial studies have clarified the aPDT efficacy of our photosensitizing hydrogels incorporating cyclodextrin/porphyrin constructs.