In-silico Modulation of the Irinotecan Release from a Functionalized MCM-41 Support

The release rate of a drug molecule from a porous support depends on a large number of factors, including support characteristics, surface functionalization (procedure and linker type), drug features, biological receptor fluid characteristics, and release conditions. Model-based (in-silico) modulation of the release rate through influential parameters can help in designing an optimized delivery system for a specific drug action. To prevent biased predictions, a dynamic mechanism-based model was adopted, by including kinetic terms related to surface adsorption-desorption, diffusion in pores, and external diffusion of the drug to the body fluid. Exemplification is made for the case of a functionalized silica MCM-41 support with a tunable pore size distribution and functionalization possibilities with hydrophobic (triethoxyvinylsilane, VTES) or hydrophilic (3-aminopropyl triethoxysilane, APTES) linkers. Variation of several structural parameters, referring to the average pore size, initial drug load, and linker proportion on a bi-functionalized support, pointed out the strong nonlinear relationships between the process variables and the release rate.