Fabrication of CaCO3-Coated Vesicles by Biomineralization and Their Application as Carriers of Drug Delivery Systems

Abstract

We fabricated CaCO3-coated vesicles as drug carriers that release their cargo under a weakly acidic condition. We designed and synthesized a peptide lipid containing the Val-His-Val-Glu-Val-Ser sequence as the hydrophilic part, and with two palmitoyl groups at the N-terminal as the anchor groups of the lipid bilayer membrane. Vesicles embedded with the peptide lipids were prepared. The CaCO3 coating of the vesicle surface was performed by the mineralization induced by the embedded peptide lipid. The peptide lipid produced the mineral source, CO32−, for CaCO3 mineralization through the hydrolysis of urea. We investigated the structure of the obtained CaCO3-coated vesicles using transmission electron microscopy (TEM). The vesicles retained the spherical shapes, even in vacuo. Furthermore, the vesicles had inner spaces that acted as the drug cargo, as observed by the TEM tomographic analysis. The thickness of the CaCO3 shell was estimated as ca. 20 nm. CaCO3-coated vesicles containing hydrophobic or hydrophilic drugs were prepared, and the drug release properties were examined under various pH conditions. The mineralized CaCO3 shell of the vesicle surface was dissolved under a weakly acidic condition, pH 6.0, such as in the neighborhood of cancer tissues. The degradation of the CaCO3 shell induced an effective release of the drugs. Such behavior suggests potential of the CaCO3-coated vesicles as carriers for cancer therapies.

Biomineral-Based Composite Materials in Regenerative Medicine

“…Porous calcium carbonates and phosphates have demonstrated their potential as effective drug carriers due to their biocompatibility and biodegradability [238][239][240]. Miyamaru et al designed and synthesized peptide lipids with specific sequences, which were then incorporated into vesicles and mineralized to create CaCO 3 -coated vesicles [241]. The mineralized vesicles retained their spherical shape and had inner spaces for drug cargo, with the CaCO 3 shell dissolved under weakly acidic conditions, such as a pH of 6.0 to release the encapsulated drugs, making them potential candidates for cancer therapies.…”

“…Ideally, a biomineral-based composite used in regenerative medicine should degrade at a rate that matches the rate of tissue regeneration. Biodegradability allows the release of ions or drugs such as growth factors and antibiotics that could help promote bone tissue regeneration as well [ 159 , 241 , 248 , 249 ]. However, controlling the degradation rate of these composites can be challenging.…”

Functional Nanomaterials and Polymer Nanocomposites: Current Uses and Potential Applications

“…Moreover, S. Stojanov et al [ 4 ] reported the incorporation of vaginal lactobacilli into electrospun nanofibers to achieve a prospective solid vaginal delivery system, and further, the fluorescent proteins were incorporated to differentiate them and allow their tracking in the future probiotic-delivery investigations. C. Miyamaru et al [ 5 ] developed CaCO 3 -coated vesicles by biomineralization and further their utilization as carriers of drug-delivery systems. In this Special Issue, M.B.…”