Modified Physicochemical Properties of Acidic Model Drugs Immobilized on Fe3O4Magnetic Iron Oxide Nanoparticles

Abstract

Nanoparticles are now extensively evaluated as drug carriers. The main objective of the present work was to evaluate the difference in physicochemical properties (solubility, permeability, lipophilicity) between acidic drugs immobilized on magnetic iron oxide nanoparticles and the same drugs in their unbound form. Synthesis of Fe3O4 magnetic iron oxide nanoparticles coated with (3-aminopropyl)triethoxysilane (APTES) was carried out with the chosen drugs attached. The obtained nanostructures were characterized using IR spectroscopy, atomic force microscopy (AFM), vibrating sample magnetometry (VSM) and dynamic light scattering (DLS) techniques, and physicochemical properties of the immobilized drugs were studied. The drug solubility was measured using the saturation shake-flask method. The permeability was measured using dialysis membranes, MWCO 50 kD with pores <10 nm. The lipophilicity was measured by partitioning in octanol. The drugs showed excellent solubility and permeability at low pH values (pH 2.0 and 5.0) and low solubility and permeability at higher pH values (pH 6.5 and 7.5) in comparison to the corresponding unbound drugs. The MNP[APTES]-immobilized drugs diffused to the organic phase very poorly, even in their non-ionized form (pH 2.0) and showed extremely low distribution coefficients. It was concluded that the immobilization of drugs on MNP[APTES] particles strongly modifies their physicochemical properties such as solubility, permeability and lipophilicity. This circumstance should be taken into account in designing new drug delivery systems, as the immobilization may strongly influence passive absorption. Extremely high release and dissolution rates of the tested drugs, followed by their efficient permeability through membrane pores at low pH, is the reason why the oral administration of therapeutic agents immobilized on MNPs should be considered as a method for more efficient drug delivery.