Osteotropic β-cyclodextrin for local bone regeneration

Abstract

An osteotropic alendronate-β-cyclodextrin conjugate (ALN-β-CD) was developed as a bonetargeting delivery system for improved treatment of skeletal diseases. The conjugate shows very strong binding to hydroxyapatite (HA, main component of the skeleton). Its ability in forming molecular inclusion complex with prostaglandins E 1 (PGE 1 , a potent bone anabolic agent) was confirmed by phase-solubility experiments and differential scanning calorimetry (DSC). In a bilateral rat mandible model, ALN-β-CD/PGE 1 molecular complex was shown to stimulate strong local bone anabolic reaction. In the control study, ALN-β-CD itself was also found to be bone anabolic. To investigate this finding, other control groups were studied. The histomorphometry data suggests that ALN-β-CD itself could generate more new bone at the injection site than its complex with PGE 1 . Alendronate (ALN) injection could also cause new bone formation, which locates peripheral to the site of injection. PGE 1 , saline or ethanol injections do not have anabolic effect. These findings were also confirmed by micro-CT evaluation of mandibular bones. It is clear that the bone anabolic effect of ALN-β-CD is independent of mechanical stimuli of the periosteum or ALN injection alone. Further studies are warranted to understand the working mechanism of ALN-β-CD as a bone anabolic agent.

Prolonged local antibiotics delivery from hydroxyapatite functionalised with cyclodextrin polymers

“…Being considered biologically inert, CDs have been approved by US FDA as pharmaceutical excipients for numerous drug formulations [12]. Recently, the study of Liu et al [13] even surprisingly reported that in vivo some b-CD derivative showed a robust bone anabolic effect. Therefore, CDs could be applied as drug carrier on bone substitute material for conferring antibacterial properties to them, and also probably further favor the bone regeneration.…”

Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin

“…For Van-loaded mPEG-PLGA micelle, the relative absorbance of the solutions treated and not treated with HA were 83% and 90%, which did not show statistical difference, implying no specific adhesion of mPEG-PLGA micelles to HA surface took place. Since the P-C-P bond and the hydroxyl group of the ALN play major roles in the affinity of ALN to HA, [29,30] no much difference was observed for the affinity test performed at pH 5.0 ( Figure 6B) from that at pH 7.4. Therefore, the binding affinity was not influenced by the external pH.…”

Distribution of grafted β-cyclodextrin in porous particles for bone tissue engineering

“…The interactions with other molecules may also be utilized to provide the surface with a drug release capability [13,14]. Another beneficial effect of cyclodextrins was discovered by Liu et al [15] who for some b-cyclodextrin derivatives could document an anabolic effect on bone.…”