Investigations on nanoconfinement of low-molecular antineoplastic agents into biocompatible magnetic matrices for drug targeting.

Magnetic mesoporous silica nanoparticles are employed as biocompatible matrices to host low-molecular antineoplastic drugs. 5-Fluorouracil is a well-known antimetabolite drug used to treat many malignancies: colon, rectal, breast, head and neck, pancreatic, gastric, esophageal, liver and G-U (bladder, penile, vulva, prostate), skin cancers (basal cell and keratosis). Unfortunately severe gastrointestinal, hematological, neural, cardiac and dermatological toxic effects are often registered due to its cytotoxicity. Thus, this work focuses on development of a magnetic silica nanosystem, capable of hosting high amounts of 5-fluorouracil and delivers it in a targeted manner, under the influence of external magnetic field. There are few reports on nanoconfinement of this particular small molecule antimetabolite on mesoporous silica hosts. Therefore we have investigated different ways to confine high amounts of 5-FU within amino-modified and non-modified mesopores of the silica shell, from water and ethanol, under magnetic stirring and ultrasound irradiation. Also, we have studied the adsorption process from water as a function of pH in order to rationalize drug-support interactions. It is shown that nature of the solvent has great influence on diffusion of small molecules into mesopores, which is slower from alcoholic solutions. More importantly, sonication is proven as an excellent alternative to long adsorption tests, since the time necessary to reach equilibrium is drastically reduced to 1h and higher amounts of drug may be immobilized within the mesopores of amino-modified magnetic silica nanoparticles. These results are highly important for optimization of drug immobilization process in order to attain desired release profile.