CaCO₃/Tetraethylenepentamine–Graphene Hollow Microspheres as Biocompatible Bone Drug Carriers for Controlled Release

Abstract

CaCO is one kind of important biological mineral, which widely exists in coral, shell, and other organisms. Since it is similar to bone tissue elements and has good biocompatibility, it was very suitable as a candidates for bone drug carriers. In this work, we used tetraethylenepentamine-graphene (rGO-TEPA) sheet matrices induction of CaCO mineralization and successfully constructed CaCO/rGO-TEPA drug carriers with a hollow structure and rough surface. As potential drug carriers, doxorubicin (DOX) loading and release measurements were carried out. It showed that load efficiency was 94.7% and the release efficiencies were 13.8% and 91.7% at values of pH 7.4 and 5.0. The as-prepared drug carriers showed some appealing advantages, such as the pH-sensitive release characteristics and mild storage-release behaviors. The excellent biocompatibility and nontoxicity of CaCO/rGO-TEPA hybrid microspheres were tested by the cell viability of mouse preosteoblast cells (MC3T3-E1). And cytotoxicity with human osteosarcoma cells (MG-63) was carried out to demonstrate the drug release effect in the cells system. Therefore, the CaCO/rGO-TEPA hybrid microspheres would be a competitive alternative in bone drug carriers.

<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

“…GDs could be introduced into different kinds of substrates, such as metals, [130][131][132] inorganic nonmetals, [133][134][135][136] natural polymers [137][138][139] and synthetic polymers [140][141][142][143] to prepare bone repair materials with improved performance, as shown in Table 3. In this subsection, the updated progress on research and development of those materials was reviewed.…”

“…In the composition of bone, inorganic substances such as hydroxyapatite accounted for a large proportion, so whether it could stimulate the biomineralization of inorganic substances in natural bone was regarded as an important index in the process of bone repair. [133][134][135][136] In the past, inorganic/organic composite scaffolds based on polymers were a common choice for bone repair, but the agglomeration of inorganic particles affected their overall stability and bioactivity. Therefore, the introduction of GDs could solve the problems.…”

“… / Excellent bactericidal activity and osteogenic activity [ 131 ] Magnesium Mg powder and 0.1wt% graphene nanosheets were dispersed by ball mill and then sintered. Micron particles Improving hardness and corrosion resistance / [ 132 ] Inorganic substance Hydroxyapatite Preparation of GO/chitosan/nHAP by in-situ synthesis and microwave-assisted method 3D porous scaffold Better dispersion and remarkable strength Significantly improving MC3T3-E1 cells viability [ 133 ] Calcium phosphate Liquid-phase and powder-phase mixing Rough microporous Higher stability, injectability and rheology Increasing the survival rate of BMSCs slightly [ 134 ] Calcium carbonate CaCl 2 /rGO and Na 2 CO 3 aqueous solution reaction Hollow microsphere Sensitive release characteristics of pH No cytotoxicity [ 135 ] Tricalcium silicate Liquid-phase and powder-phase mixing Spherical particles with rough and porous surface Higher compressive strength and lower pH value Excellent ability of MC3T3-E1 cells proliferation and antibacterial [ 136 ] Natural polymer Chitosan In situ crystallization process (acetic acid, Ca (NO 3 ) 2 and K 2 HPO 4 aqueous solution) 3D porous bone-like hierarchical structure Biodegradability and appropriate water absorption and water retention Excellent biological activity and ability to induce bone regeneration in situ [ …”

Black phosphorus-based 2D materials for bone therapy

“…Compared with ordinary dosage form drugs, microspheres can improve the stability of drugs [ 183 ], reduce the stimulation of the gastrointestinal tract [ 184 ], enhance the controlled release and delivery to the targeted region [ 185 , 186 ]. For example, Li et al used tetraethylenepentamine-graphene (rGO-TEPA) to induce CaCO 3 mineralization and successfully constructed a CaCO 3 /rGO-TEPA drug carrier with a hollow structure and rough surface to achieve DOX loading and sustained release, which can regulate release and promote anti-tumor treatment through pH response [ 187 ]. In addition to being an excellent controlled-release carrier, microspheres can be packaged individually or combined with other materials to make a porous 3D structure serving as tissue engineering scaffolds [ 188 , 189 ].…”

Synthesis of Polymer Assembled Mesoporous CaCO3 Nanoparticles for Molecular Targeting and pH-Responsive Controlled Drug Release

“…MTT Assays. According to the previous report [37,38], the cell viability of the functionalized DOX-MCNs mesoporous carrier was assessed using the MTT cell analysis. HeLa cells were cultured in DMEM supplemented with 10% fetal bovine serum (FBS), penicillin (100 units• mL −1 ), streptomycin (100 mg•mL −1 ) and 5% CO 2 .…”