WS01.6 The rational design of nanomedicines for chronic pulmonary infection treatment: Does size really matter?

Abstract

Objectives Several studies showed that encapsulating antibiotics in nanoparticles can improve the killing of biofilm bacteria. To ensure maximal delivery of the antibiotic to the infection site, the nanoparticle's physicochemical characteristics need to be optimized. In this study, the influence of the nanoparticle size on their penetration into dense biofilm clusters was evaluated. Methods A confocal microscopy method was developed to measure the percentage of fluorescent polystyrene nanoparticles able to penetrate into P. aeruginosa LMG 27622 and B. multivorans LMG 18825 biofilm clusters. The diameter of the particles ranged from 40 to 555 nm. Liposomes of 70 and 100 nm were also evaluated, as this particle type represents a widely used drug delivery nanocarrier. Results As expected, the penetration of the particles into the biofilm clusters decreased as the particle size increased. Slight differences were observed between both biofilms. For the B. multivorans biofilm, a sharp decrease in particle penetration was seen for particles larger than 130 nm. A more gradual decrease was seen in P. aeruginosa biofilms, which showed an overall lower particle penetration compared to B. multivorans. The cut-off for maximal nanoparticle penetration was also lower, around 100 nm. The liposomes were found to correlate well with the results obtained using polystyrene particles. Conclusion For P. aeruginosa and B. multivorans biofilms, nanoparticles of ±100 nm are optimal as this size allows for maximal biofilm penetration and sufficient loading of antimicrobial agents. Furthermore, the polystyrene particles showed to be a suitable model for the prediction of liposome penetration.