title: Osteotropic beta-cyclodextrin for local bone regeneration.
abstract: An osteotropic alendronate-beta-cyclodextrin conjugate (ALN-beta-CD) was developed as a bone-targeting 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 prostaglandin 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-beta-CD/PGE(1) molecular complex was shown to stimulate strong local bone anabolic reaction. In the control study, ALN-beta-CD itself was also found to be bone anabolic. To investigate this finding, other control groups were studied. The histomorphometry data suggest that ALN-beta-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-beta-CD is independent of mechanical stimuli of the periosteum or ALN injection alone. Further studies are warranted to understand the working mechanism of ALN-beta-CD as a bone anabolic agent.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, COP 3026, Omaha, NE 68198-6025, USA.
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Wiswall
authors.forename: John E
authors.initials: JE
authors.lastname: Rutledge
authors.forename: Mohammed P
authors.initials: MP
authors.lastname: Akhter
authors.forename: Diane M
authors.initials: DM
authors.lastname: Cullen
authors.forename: Richard A
authors.initials: RA
authors.lastname: Reinhardt
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000527:Alprostadil; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002152:Calorimetry, Differential Scanning; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D008903:Minerals / Q000737:chemistry; D010024:Osteoporosis / Q000473:pathology; D051381:Rats; D012995:Solubility; D014057:Tomography, X-Ray Computed; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D008903:Minerals; D047392:beta-Cyclodextrins; D000527:Alprostadil; C031215:betadex