RESUMO
Silica@zirconia@poly(malic acid) nanocarriers of 110 nm mean diameter were designed, synthesized and characterized for the targeted delivery of diagnostic and therapeutic 99mTc to folate-overexpressing tumors. An important achievement was that a multifunctional l-(-)-malic-acid-based copolymer was formed in situ at the surface of the inorganic cores in a single synthetic step incorporating l-(-)-malic acid, ß-cyclodextrin rings, folic acid moieties, and polyethylene glycol chains. Morphological and in-depth structural analysis of the particles proved their core@shell structure. Stability experiments in aqueous media evidenced that stable suspensions can be obtained from the lyophilized powder in 10 mM phosphate buffer at pH 7.4. During 14-day degradation experiments, the nanoparticles were found to be slowly dissolving (including inorganic core) in saline and also in total cell medium. An in vitro toxicity assay on hepatocytes showed a concentration-dependent decrease of cell viability down to 63 ± 1% at the highest applied concentration (0.5 mg ml-1). Proof of concept experiments of technetium-99m radiolabelling and in vivo labelling stability are presented.
RESUMO
Porous, fluorescent zirconia particles of nearly 380 nm diameter were prepared without template molecules or labeling dyes. The porous structure is the result of aggregation-induced particle formation. The inherent fluorescence is assigned to coordinatively unsaturated Zr4+ ions at the sol-gel derived ZrO2 surface. After physico-chemical characterization of the native zirconia particles carboxyl and/or amine bearing drug molecules (d,l-α-difluoromethylornithine - DFMO, ursolic acid - UA and doxorubicin - DOX) were adsorbed onto their surface, and the products were analyzed with Fourier-transform infrared spectroscopy (FTIR), thermogravimetry (TG), small-angle X-ray scattering (SAXS), fluorimetry and zeta potential vs. pH measurements. We have found that DOX complexes coordinatively unsaturated Zr4+ ions without dislocating them, while carboxyl-bearing drugs interact with basic surface Zr-OH sites eliminating some of the carbonate species. The adsorption of UA at the zirconia surface shifts considerably the isoelectric point of the surface and thus provides kinetic stability to the particles at physiological pH. An in vivo biodistribution study in two healthy dogs performed by SPECT/CT detection after 99mTc labeling of the nanocarriers has shown the possibility of drug delivery application.
