Sistemas transportadores para el control de dosificación de cisplatino

Abstract

Cisplatin is a chemotherapeutic drug often used for treatment of several types of sarcoma, lymphoma and carcinoma; nevertheless, its high toxicity calls for a means of controlled drug delivery so to minimize collateral damage. To this end, we have investigated three types of inorganic porous solids: mesoporous MCM41 type silica (pristine, as well as functionalized with either amino or carboxy groups), polyacrylic acid functionalized silica and hydroxyapatite. These materials were prepared following previous literature reports and characterized by powder X-ray diffraction, electron microscopy, nitrogen adsorption at 77 K (to determine surface area and porosity), thermogravimetry, and FT-IR and CP-MAS NMR spectroscopy. Cisplatin loading was accomplished by soaking the porous solids in an aqueous solution of the drug (1 mg/ml) for 24 h at 37ºC. In vitro drug delivery tests were carried out by immersing the loaded samples into a stirred isotonic saline solution (0.9% NaCl) kept at 37ºC. The amount of cisplatin released was quantified by UV-Vis spectroscopy of the complex formed with o-phenylendiamine. Among mesoporous MCM41 type materials, the amino-functionalized sample showed a higher cisplatin uptake (61.4 mg per gram) than the other two samples (8.7 mg/g for pure MCM41 and 14.7 mg/g for carboxy-functionalized MCM41). However, the carboxy-functionalized sample showed a more favourable drug release kinetics, which lasted for about 140 h while it ended after only 60 h in the case of both pure MCM41 and amino-functionalized MCM41. On the other hand, the polyacrylic acid functionalized silica showed a kinetics of drug release similar to that of carboxyfunctionalized MCM41, while affording a greater cisplatin uptake (31.0 mg/g). Hydroxyapatite showed an even larger drug uptake (98.4 mg/g), but also a faster drug delivery (which ended after only 80 h). This is probably related to the larger pore diameter (5-40 nm) of the hydroxyapatite sample, as compared to 2.5-5 nm in the case of silica samples.