Biocompatible porous metal-organic framework nanoparticles based on Fe or Zr for gentamicin vectorization

Due to their high porosity and versatile composition and structure, nanoscaled Metal-Organic Frameworks (nanoMOFs) have been recently proposed as novel drug delivery systems, and have been demonstrated to have important capacities and potential for controlled release of different active ingredients. Gentamicin (GM; a broad spectrum aminoglycoside antibiotic indicated in bacterial septicemia therapy) has great therapeutic interest, but the associated bioavailability and toxicity drawbacks accompanying high doses and repeated administration of this free drug make its encapsulation inside new nanocarriers necessary. GM encapsulation within two different porous biofriendly Fe and Zr-carboxylates nanoMOFs was performed by a simple impregnation method, with full characterization of the resulting GM-containing solid using a large panel of techniques (X ray powder diffraction-XRPD, Fourier transform infrared spectroscopy-FTIR, thermogravimetric analysis-TGA, N-2 sorption, scanning electron microscopy-SEM, dynamic light scattering-DLS, zeta-potential, fluorescence spectroscopy and molecular simulations). High reproducible encapsulation rates, reaching 600 mu g of GM per mg of formulation, were obtained using the biocompatible mesoporous iron(III) trimesate nanoparticles (NPs) MIL-100(Fe) (MIL: Materials from Institut Lavoisier). In vitro GM delivery studies were also carried out using different oral and intravenous simulated physiological conditions, with complete antibiotic release within 8 h when using protein free media, but lower release rates in the presence of proteins. Furthermore, in vitro toxicity of GM-containing MIL-100(Fe) NPs was investigated on two different cell lines: a monocyte from leukemia (THP-1) and adherent fibroblastoid cells (NIH/3T3). These nanoMOFs had a low cytotoxic profile with IC50 values up to 1 mg.mL(-1), ensuring adequate cell proliferation after 24 h. Finally, antibacterial activity studies were carried out on two Gram-positive bacteria and one Gram-negative bacterium: S. aureus, S. epidermidis and P. aeruginosa, respectively. GM-loaded MIL-100(Fe) NPs exhibited the same activity as free GM, confirming that the antibiotic activity of the released GM was conserved.