PH- and redox-responsive hybrid porous CaCO3 microparticles based on cyclodextrin for loading three probes all at once

Abstract

Drug molecules are often insoluble or poorly soluble in physiological medium and they may accumulate in fat tissues leading to drawbacks for the patient's recovery. Moreover to avoid side-effects, selective release of the drug is of major interest. In this context, we propose to combine the advantageous features of both porous and negatively charged surfaces of calcium carbonate (CaCO3) particles and host molecules (cyclodextrin, CD) for developing carrier enabling the loading of both hydrophobic and hydrophilic (ionic) several molecules all at once. Porous calcium carbonate particles present highly benefits for biological purposes because of their large surface area and their high stability in neutral media. CD presents the advantage of owing hydrophilic exterior and a less polar cavity in the center. For instance, hydrophobic drug/CD can form inclusion complexes in aqueous media. We have loaded a hydrophobic molecule, namely tocopherol acetate, inside the CD cavity and an ionic probe (rhodamine b) inside the porosity of the CaCO3. A controlled and selective release of the probe is finally evidenced according to the pH of the medium (pH 5 and 7.4). We also propose an approach combining the thiol/disulfide chemistry and the layer-by-layer process to load a third probe which is then selectively released under reducing conditions. Our strategy enables thus to easily load three probes all at once and to control their release according to the applied stimulus (pH or redox condition).