Table 2.
Systems Containing Bisphosphonates That Can be Used to Develop Scaffolds for Bone Tissue Engineering
| Delivery systems that can be used as scaffolds | BP incorporate | Experimental trial | BP release quantification | Most important contributions | References |
|---|---|---|---|---|---|
| Chitosan microspheres | Pamidronate | In vitro, In vivo | - | The release of BP from microspheres was faster in vitro than in vivo. After implantation, drugs exhibited a relatively increased disposition in the adjacent tibia. | 139 |
| Poly-D,L-lactic acid (PDLLA) scaffolds | Pamidronate | In vivo | - | PDLLA pellets containing Bone Morphogenetic Protein (BMP) and PAM showed an increase in bone formation after 3 weeks when low doses of PAM were used (0.02 mg). Polymer degradation remained until 8 weeks. | 147 |
| Mesoporous silica-based materials (MCM41, SBA15) | Alendronate | In vitro release of Alendronate | - | Amine functionalization on mesopores enhances 3 times the incorporation of ALN and reduces the mesopore surface area. The diffusive behavior of the absorbed molecule through the mesopores can be calculated using a zero-order or lineal model. | 134 |
| Mesoporous silica-based materials (SBA15) | Alendronate | In vitro release of Alendronate | RP-HPLC | Mesopores functionalizatiwith aminopropyl groups was made using a catalytic or an anhydrous procedure. The catalytic method induces a more gradual ALN loading (approximately 3 mg ALN/25 mg SiO2) that depends on the functionalization degree and offers a better control in the release of ALN molecules showing a deviation from the theoretical first-order behavior. | 135 |
| HA-coated starch scaffold | Clodronate | In vitro | HPLC-UV detection | The microhardness increases by increasing the BP concentration on the coating (from 0.004 to 1 mg/cm2). A zero-order kinetic was observed during 14 days at pH 7.4. The CLO that is incorporated promoted osteoblast-like cell adhesion, and it has influenced cellular proliferation in a way dependent of the concentration, being 0.02 mg/cm2 of BP the ideal concentration for enhancing cell viability. | 138 |
| PLGA/HA microspheric system | Alendronate | In vitro | Spectrophotometrically, as a Fe(III) complex | ALN was encapsulated using a single emulsion method, which showed a higher encapsulation efficiency (about 90%) than the double emulsion one. A controlled zero-order release during 30 days was achieved, without a remarkable initial burst effect: composites with 50% of HA showed a better controlled release. Inhibition on the growth of macrophages and enhancement in the proliferation of osteoblasts were observed. | 7 |
| PCL fibres loaded with HA and BP | Clodronate | In vitro characterization | - | PCL fiber scaffolds were developed by using electro- and wet-spinning techniques and loaded with HA nanoparticles, which had CLO linked (about 75 mg ALN/250 mg HA). Release kinetics of CLO, through the tuning of fiber dimensions and mesh porosity, could be controlled. | 140 |
| PLA/PEO-ZOL/PLA nanofiber meshes | Zoledronate | In vitro release of Zoledronate | HPLC-UV detection | The sandwich structure-like meshes show the main advantages of facile preparation condition and the possibility of including hydrophobic or hydrophilic drugs. In vitro experiments revealed that with an increase in the thickness of inner drug-loaded mesh, the drug release rate and initial burst release decreased. | 141 |
| HA microspheric system | Alendronate | In vitro | Spectrophotometrically, as a Fe(III) complex | They fabricated a microsphere-type carrier where ALN loading and microsphere formation can occur through a simultaneous process, and the loading content was much higher than other CaP carrier systems (approximately 19.5 wt.% ALN). A controlled drug release for 40 days was achieved, which was dependent on the dissolution rate of the HA microspheres. The release showed linear kinetics, except for a burst effect during the initial 24 h. In addition, the inhibition of osteoclast formation was observed. | 40 |
BP, bisphosphonates; RP, reverse phase; ALN, alendronate; HA, hydroxyapatite; PCL, poly(ε-caprolactone); CLO, clodronate; PLA, Poly (L-lactic acid); PEO, polyethylene oxide; ZOL, Zoledronate; CaP, calcium phosphates; UV, ultraviolet.