Composite Magnetite and Protein Containing CaCO₃ Crystals. External Manipulation and Vaterite → Calcite Recrystallization-Mediated Release Performance

Abstract

Biocompatibility and high loading capacity of mesoporous CaCO3 vaterite crystals give an option to utilize the polycrystals for a wide range of (bio)applications. Formation and transformations of calcium carbonate polymorphs have been studied for decades, aimed at both basic and applied research interests. Here, composite multilayer-coated calcium carbonate polycrystals containing Fe3O4 magnetite nanoparticles and model protein lysozyme are fabricated. The structure of the composite polycrystals and vaterite → calcite recrystallization kinetics are studied. The recrystallization results in release of both loaded protein and Fe3O4 nanoparticles (magnetic manipulation is thus lost). Fe3O4 nanoparticles enhance the recrystallization that can be induced by reduction of the local pH with citric acid and reduction of the polycrystal crystallinity. Oppositely, the layer-by-layer assembled poly(allylamine hydrochloride)/poly(sodium styrenesulfonate) polyelectrolyte coating significantly inhibits the vaterite → calcite recrystallization (from hours to days) most likely due to suppression of the ion exchange giving an option to easily tune the release kinetics for a wide time scale, for example, for prolonged release. Moreover, the recrystallization of the coated crystals results in formulation of multilayer capsules keeping the feature of external manipulation. This study can help to design multifunctional microstructures with tailor-made characteristics for loading and controlled release as well as for external manipulation.

In vivo optical monitoring of transcutaneous delivery of calcium carbonate microcontainers

“…Targeted delivery of biodegradable microspheres as well as other carriers providing sustained release of their contents are actual tasks for many medical applications and are discussed widely in literature [2,13,15,[17][18][19][20]. However, penetration of carriers through skin epidermal barrier remains a significant problem.…”

“…In Ref [22] ex vivo pig skin was studied as we punctured rat skin in vivo. Biodegradability of microcarriers is important advantage [18][19][20]. Time stability of CaCO 3 microcontainers containing Fe 3 O 4 nanoparticles with and without polyelectrolyte shell in water was studied in [20].…”

“…Biodegradability of microcarriers is important advantage [18][19][20]. Time stability of CaCO 3 microcontainers containing Fe 3 O 4 nanoparticles with and without polyelectrolyte shell in water was studied in [20]. Recently, medical formulation was encapsulated in 600 μm long microneedles composed of carboxymethylcellulose and trehalose, which could be dissolved in body fluid [18].…”

Loading Capacity versus Enzyme Activity in Anisotropic and Spherical Calcium Carbonate Microparticles

“…Among the three polymorphs (calcite, aragonite, or vaterite) of CaCO 3 , vaterite is thermodynamically the least stable one 41 . However, for drug delivery applications, it is an attractive candidate since vaterite particles are not toxic 38 and highly porous capable of immobilizing many small 39,42,43 and large molecules [44][45][46][47] into their interior structure 48 . In other application areas such as biomineralization or nanomaterial processing, CaCO 3 particles are utilized in a diverse range of shapes because their crystallization mechanism can be easily altered using organic additives [49][50][51][52] .…”

Carriers for the tunable release of therapeutics: etymological classification and examples

“…Another direction worth exploring belongs to the exploitation of transitory, metastable, non-equilibrium states for the kinetic control of release patterns. Polymorphic transitions have been used to mediate drug release [99], but no tunable effects have been reported so far. Particle shell-to-core volume ratio is another parameter that has been used to produce different release profiles; however, the correlation between this parameter and release rate was rather volatile, not allowing for the tunable effect [100].…”