Bodipy-Loaded Micelles Based on Polylactide as Surface Coating for Photodynamic Control of Staphylococcus aureus

Abstract

Decontaminating coating systems (DCSs) represent a challenge against pathogenic bacteria that may colonize hospital surfaces, causing several important infections. In this respect, surface coatings comprising photosensitizers (PSs) are promising but still controversial for several limitations. PSs act through a mechanism of antimicrobial photodynamic inactivation (aPDI) due to formation of reactive oxygen species (ROS) after light irradiation. However, ROS are partially deactivated during their diffusion through a coating matrix; moreover, coatings should allow oxygen penetration that in contact with the activated PS would generate 1O2, an active specie against bacteria. In the attempt to circumvent such constraints, we report a spray DCS made of micelles loaded with a PS belonging to the BODIPY family (2,6-diiodo-1,3,5,7-tetramethyl-8-(2,6-dichlorophenyl)-4,4′-difluoroboradiazaindacene) that is released in a controlled manner and then activated outside the coating. For this aim, we synthesized several amphiphilic copolymers (mPEG–(PLA)n), which form micelles, and established the most stable supramolecular system in terms of critical micelle concentration (CMC) and ∆Gf values. We found that micelles obtained from mPEG–(PLLA)2 were the most thermodynamically stable and able to release BODIPY in a relatively short period of time (about 80% in 6 h). Interestingly, the BODIPY released showed excellent activity against Staphylococcus aureus even at micromolar concentrations.

Antimicrobial Photodynamic Therapy: Latest Developments with a Focus on Combinatory Strategies

“…In addition to recent examples such as the hypericin loaded liposomes against Gram(+) bacteria [282][283][284][285][286], another emerging and promising alternative includes the development of modified liposome-like derivatives labeled either as "ethosomes", "transfersomes", or "invasomes", which can be briefly described as ultra-deformable vesicular carriers with upgraded transdermal penetration and increased permeability into the skin for the PSs compared with conventional liposomes [287][288][289][290]. On the other hand, recently reported aPDT micellar systems refer to micelles loaded with various hydrophobic PSs such as curcumin, BODIPY, porphyrins, hypocrellin A, or hypericin among others [121,[291][292][293]. Furthermore, solid lipid NPs (SLN) composed of solid biodegradable lipids have been recently highlighted as delivery systems used for actual mRNA COVID-19 vaccines [294], but they also have been reported as transporters for curcumin for the treatment of oral mucosal infection [121].…”

“…Among examples, an aPDT system of polymeric micelles, fabricated from methoxy-PEG and PCL and loaded with the hydrophobic PS curcumin and ketoconazole for the PDI of fungal biofilms, has been reported with an increased water solubility and controlled release of the PSs on display [380]. Additionally, Caruso et al recently reported the synthesis of thermodynamically stable PEG-PLA micelles for efficient aPDI of S. aureus, suggesting that this delivery system is promising in aPDI applications, which also reduces toxicity compared with pure PSs [291]. Moreover, a significant advantage of polymeric micelles compared with lipid-based micelles resides notably in the adjustability of properties by individual design of the polymer and membrane surface with respect to the selected application.…”

Photoinactivation of Pseudomonas aeruginosa Biofilm by Dicationic Diaryl-Porphyrin

“…PDT provoked a certain damage to embedded PAO1 cells, suggesting that they could be more sensitive to other antimicrobial agents delivered upon photodynamic treatment. The embedding of porphyrins in nanoparticles or polymeric coatings could be exploited both for skin disinfection and surface sanitization [48,49].…”

BODIPYs in PDT: A Journey through the Most Interesting Molecules Produced in the Last 10 Years

“…Even in the case of BODIPYs this type of approach is extremely important for their application in PDT [ 40 , 71 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ].…”