Full length articleControlling nucleation and growth of nano-CaCO3 via CO2 sequestration by a calcium alkoxide solution to produce nanocomposites for drug delivery applications

Calcium carbonate is an extremely attractive material in a plethora of biomedical applications. Intensive efforts have recently been made to achieve the control over its nucleation and subsequent aggregation, growth and crystallization; focusing on bringing insight into the role of precursors, solvents and templates. Having analyzed the recently acquired knowledge, we addressed this challenge using CO2 sequestration synthesis, using an unusual reactant, a solution of calcium ethoxide, Ca(OC2H5)2, as precursor. By tailoring the reaction conditions, it was possible to produce extremely small and rather size-uniform single-phase calcite CaCO3 nanoparticles, forming sols and subsequently gels in the applied medium. According to DLS and nanoparticle tracking analysis the particles are only to a minor extent aggregated in the mother liquor and can form transparent gels on concentration in less polar media, but produce large aggregates 400-800 nm in size when dried and subsequently transferred to aqueous media. Complete drying of solutions renders xerogel type materials with only moderate active surface area, as identified by nitrogen adsorption, due to aggregation with development of densified surface layers. Such behaviour is typical for the sol-gel synthesis of particles possessing enhanced surface reactivity. The aggregation on drying was used to produce hybrid nanocomposites, with the hydrophobic model component, β-carotene, introduced in solution in a non-polar co-solvent and model medicine - ibuprofen. The obtained nanocomposite particles, characterized by SEM, TEM, XRD, AFM and FTIR studies, are hierarchically structured spheroidal aggregates about 200 nm in size with uniform distribution of the organic components present in the amorphous state. The composite particles are stable in neutral aqueous environments but are readily dissolved in acidic medium or even in PBS at pH = 7.40, releasing the hydrophobic organic component in the form of a relatively stable colloid solution. Efficient release of ibuprofen as model drug was achieved in both acidic and PBS medium and could be slowed down by the addition of β-carotene as hydrophobic component.Statement of SignificanceThe proposed sol-gel synthesis of CaCO3 proved to create unprecedented size of CaCO3 nanoparticles with striking size uniformity. The obtained results clearly demonstrate their ability to incorporate hydrophobic components in a nanocomposite matrix converting them into amorphous nano sized particles, building stable colloids via release in acidic medium. Transfer of a sol produced in organic medium into water in the presence of albumen surfactant results in relatively uniform micro particles about 1 μm size. The obtained materials show characteristics attractive for use in drug delivery and potentially also a variety of other industrial applications.

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