Preparation of bifunctional hybrid mesoporous silica potentially useful for drug targeting

Abstract

Bifunctional hybrid mesoporous silica potentially useful for drug targeting has been synthesized starting from neutral surfactant-templated mesoporous silica. A receptor specific ligand folic acid, in principle able to be recognized from specific tissues, has been covalently coupled on the external function of as-synthesized mesoporous silica thanks to the presence of aminopropyl groups. A series of hybrid materials useful to investigate the complex structure of folate-derivatized materials have been developed starting from a silica gel substrate derivatized with amino-propyl functionality and successively coupled to folic or heptanoic acid. FT-IR spectroscopy as well as NMR results unambigously shows that amide covalent bond is successfully achieved through the use of carbodiimides type reagents, typically used in peptide synthesis. Folic acid has been retained on the surface of functional mesoporous silica both in the case in which carbodiimide reactant is used and for the blank without carbodiimide; in the latter case it is removed after HCl treatment showing that folic acid was retained by electrostatic interaction and by van der Waals forces. One of the materials, after surfactant extraction, has been charged with cisplatin, an anticancer agent. The diffusion profile in a simulated body fluid shows that cisplatin is gradually released during 6 h.