Mesoporous Bioactive Glasses Equipped with Stimuli-Responsive Molecular Gates for Controlled Delivery of Levofloxacin against Bacteria

Abstract

18944 18951 24 71 ; S ; Candel, I., Aznar, E., Mondragón, L., Torre, C. de la, Martínez-Máñez, R., Sancenón, F., … Parra, M. (2012). Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles. Nanoscale, 4(22), 7237. doi:10.1039/c2nr32062b ; [EN] An increase of bone diseases incidence has boosted the study of ceramic biomaterials as potential osteo-inductive scaffolds. In particular, mesoporous bioactive glasses have demonstrated to possess a broad application in the bone regeneration field, due their osteo-regenerative capability and their ability to release drugs from the mesoporous structure. These special features have been studied as an option to fight against bone infection, which is one of the most common problems regarding bone regeneration therapies. In this work, a mesoporous bioglass functionalized with polyamines and capped with adenosine triphosphate (ATP) as the molecular gate was developed for the controlled release of the antibiotic levofloxacin. Phosphate bonds of ATP were hydrolyzed in the presence of acid phosphatase (APase), the concentration of which is significantly increased in bone infection due to the activation of bone resorption processes. The solid was characterized and tested successfully against bacteria. The final gated solid induced bacterial death only in the presence of acid phosphatase. Additionally, it was demonstrated that the solid is not toxic against human cells. The double function of the prepared material as a drug delivery system and bone regeneration enhancer confirms the possible development of a new approach in the tissue engineering field, in which controlled release of therapeutic agents can be finely tuned and, at the same time, osteoinduction is favored. The authors thank the Spanish Government for projects MAT2015-64139-C04-01-R, MAT2015-64831-R and MAT2016-75611-R (AEI/FEDER, UE). Generalitat Valenciana (project PROMETEOII/2014/047) and CIBER-BBN (project SPRING) are also ...