Fabrication of CaCO(3)-Coated Vesicles by Biomineralization and Their Application as Carriers of Drug Delivery Systems

We fabricated CaCO(3)-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 CaCO(3) coating of the vesicle surface was performed by the mineralization induced by the embedded peptide lipid. The peptide lipid produced the mineral source, CO(3)(2−), for CaCO(3) mineralization through the hydrolysis of urea. We investigated the structure of the obtained CaCO(3)-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 CaCO(3) shell was estimated as ca. 20 nm. CaCO(3)-coated vesicles containing hydrophobic or hydrophilic drugs were prepared, and the drug release properties were examined under various pH conditions. The mineralized CaCO(3) 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 CaCO(3) shell induced an effective release of the drugs. Such behavior suggests potential of the CaCO(3)-coated vesicles as carriers for cancer therapies.