Design of polymeric carriers to enhance antimicrobial photodynamic inactivation

Abstract

Mixed polymeric micelles are a promising tool for the design of nanocarriers with pharmaceutical properties. These micellar systems allow reversing numerous properties of lipophilic drugs. Particularly, when applied to transport photosensitizers (PSs), they give rise to a wide variety of nanophotosensitizers (nPSs). These compounds are used to inactivate numerous bacteria resistant to conventional antibiotics. This research proposes the development of new mixed micelles, with better properties than simple micelles, for the trapping of Neutral Red (NR) and its monobrominated derivative (NRBr). Based on the combination of Pluronic P-123 with Pluronic F- 108, Pluronic L-61 and Tween 80, 15 binary micellar systems were obtained. These mixed micelles presented a single population of homogeneous particles, with a diameter less than 70 nm. Moreover, several mixed micelles show smaller CMC than the simple system. These properties are predictors of high micellar stability and good anti-dilution properties, favoring their drug delivery applications. For these reasons, were loaded with NR and NRBr, showing good encapsulation efficiency. The 30 new nPSs presented an adequate size for pharmaceutical use and markedly enhanced the photochemical reactivity of the free PSs. Many of the mixed micellar systems showed greater production of singlet oxygen than the simple micelles of Pluronic P-123. Furthermore, all micellar systems increased the chemical stability of NRBr, which degrades in pH 7.4 buffer solution. Finally, all nPSs presented greater phototoxic activity against methicillin-resistant Staphylococcus aureus than free PSs. The nPSs formed by P-123: F-108 (90:10) +NR, P-123: F-108 (90:10) +NRBr, P-123: L-61 (80:20) +NRBr and P 123: T80 (80:20) +NRBr caused greater photodynamic inactivation of the microorganism than simple P-123 micellar systems. These nPSs could be considered excellent candidates for application in the treatment of infections caused by bacteria resistant to antibiotics.